Review Article The Protective Role of Antioxidants in the...

Review ArticleThe Protective Role of Antioxidants in the Defence againstROSRNS-Mediated Environmental Pollution

Borut Poljšak and Rok Fink

Faculty of Health Sciences University of Ljubljana Zdravstvena pot 5 SI-1000 Ljubljana Slovenia

Correspondence should be addressed to Rok Fink rokfinkzfuni-ljsi

Received 21 April 2014 Revised 3 June 2014 Accepted 17 June 2014 Published 20 July 2014

Academic Editor Felipe Dal-Pizzol

Copyright copy 2014 B Poljsak and R Fink This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants such as ionising andnonionising radiation ultraviolet radiation elevated concentrations of ozone nitrogen oxides sulphur dioxide cigarette smokeasbestos particulate matter pesticides dioxins and furans polycyclic aromatic hydrocarbons and many other compounds presentin the environment It appears that increased oxidativenitrosative stress is often neglected mechanism by which environmentalpollutants affect human health Oxidation of and oxidative damage to cellular components and biomolecules have been suggestedto be involved in the aetiology of several chronic diseases including cancer cardiovascular disease cataracts age-related maculardegeneration and aging Several studies have demonstrated that the human body can alleviate oxidative stress using exogenousantioxidants However not all dietary antioxidant supplements display protective effects for example 120573-carotene for lung cancerprevention in smokers or tocopherols for photooxidative stress In this review we explore the increases in oxidative stress causedby exposure to environmental pollutants and the protective effects of antioxidants

1 Introduction

Many environmental pollutants are sources of several reactivespecies (RS) RS is a collective term that includes both oxygenradicals and other reactive oxygen and nitrogen species(ROSRNS) Free radicals important for living organismsinclude hydroxyl (OH∙) superoxide (O

2

∙minus) nitric oxide(NO∙) thyl (RS∙) and peroxyl (RO

2

∙) radical Peroxynitrite(ONOOminus) hypochlorous acid (HOCl) hydrogen peroxide(H2

O2

) singlet oxygen (1O2

) and ozone (O3

) are not freeradicals but can easily lead to free radical reactions in livingorganisms The term reactive oxygen species (ROS) is oftenused to include not only free radicals but also the nonradicals(eg 1O

2

ONOOminusH2

O2

O3

) [1]There is strong evidence that RS is involved in oxidative

nitrosative stress (ONS) as a common mechanism by whichseveral environmental pollutants induce damage Oxidativestress can be defined as an excessive amount of RS which isthe net result of an imbalance between production and des-truction of RS (the latter is regulated by antioxidant defences)

Oxidative stress is a consequence of an increased generationof RS andor reduced physiological activity of antioxidantdefences against RS Environmental pollutants stimulate avariety of mechanisms of toxicity on molecular level andoxidative stress seems to be the common denominatorleading to the damage to cellular membrane lipids DNA andproteins [2] aswell asmodulation of antioxidant enzymes RSare due to their high reactivity (eg hydroxyl radical forma-tion) prone to cause damage to any type of molecule withinthe cell for example polyunsaturated fatty acids glutathionecertain amino acids and so forth

When the antioxidant defence in the human bodybecomes overwhelmed oxidative stress to the cellular com-ponents often occurs inducing inflammatory adaptive inju-rious and reparative processes [3] On other hand lifestyleand nutrition might play an important role against envi-ronmental oxidant exposure and damage Protection againstONS-mediated environmental pollutants can generallyoccur at two levels (i) physiochemical protection to lowerthe dose of exposure which typically cannot be accomplished

Hindawi Publishing CorporationOxidative Medicine and Cellular LongevityVolume 2014 Article ID 671539 22 pageshttpdxdoiorg1011552014671539

2 Oxidative Medicine and Cellular Longevity

by individuals living in polluted areas or (ii) physiologicalprotection to increase the antioxidative defence of the organ-ism There is growing scientific evidence that low molecular-weight antioxidants are involved in the prevention of or thedecrease in the damage caused by certain environmentalpollutants Because we have little influence on the increasinglevels of endogenous antioxidants it would be reasonableto increase the amount of exogenous antioxidants (mainlythrough ingestion) to strengthen the defensive propertiesof organisms against environmental oxidative stress Thecurrent evidence suggests that increased consumption offruits and vegetables or certain dietary supplements cansubstantially enhance the protection against many commontypes of environmentally induced ONS

2 Purpose

This review aims to determine whether antioxidants canmodulate the toxicity of environmental pollutants therebyinfluencing health and disease outcome associated withoxidative stress-induced insults Evidence will be presentedthat environmental pollution increases oxidative stress andthat dietary supplementation with antioxidants may playa role on the neutralization or buffering of the effects ofpollutants with oxidizing properties The recommendationfor the use of dietary antioxidants in areas of increasedenvironmental pollution will be discussed

This review summarises the most common and health-relevant sources of oxidative stress like air pollution radia-tion pesticides noise and household chemicals Due to spaceconstrains and a broad scientific data not all the studiescould be covered in this reviewThe reader is thus referred tosearch through provided references (and references therein)for further details on selected environmental pollutant orselected antioxidant

21 Air Pollution-Induced Oxidative Stress and Protectionagainst It The health effects of air pollution result fromminor irritation of the eyes and the upper respiratory systemto chronic respiratory disease heart and vascular diseaselung cancer and death Different studies presented in Table 1are demonstrating increased oxidative stressdamage dueto air pollutant exposure and that antioxidants could offercertain level of protection [4ndash7]

Oxygen could be presented as the leading air pollutantin regard to oxidative stress formation Molecular O

2

itselfqualifies as a free radical because it has twounpaired electronswith parallel spin in different 120587-antibonding orbitals Thisspin restriction accounts for its relative stability and paramag-netic properties O

2

is capable of accepting electrons to itsantibonding orbitals becoming ldquoreducedrdquo in the process andtherefore functioning as a strong oxidizing agent [76] Thediatomic molecule of oxygen contains two uncoupled elec-trons and can therefore undergo reduction yielding severaldifferent oxygen metabolites which are collectively calledROS Mitochondria are the main site of intracellular oxygenconsumption and the main source of ROS formation [8 1013 77] Once ROS are produced they are removed by cellular

defenses which include the enzymes superoxide dismutase(Mn-SOD CuZn-SOD and extracellular (EC)-SOD) cata-lase glutathione peroxidase peroxiredoxins and the nonen-zymatic antioxidants like glutathione (GSH) thiore-doxinascorbate 120572-tocopherol and uric acid [9 78] Since oxidativedamage of cells increases with age the increased intakeof exogenous antioxidants may support the endogenousantioxidative defense Clinical studies imply that eating a dietrich in fruits vegetables whole grains legumes and omega-3fatty acids can help humans in decreasing oxidative stress andpostponing the incidence of degenerative diseases [79]

Ozone is formed from dioxygen by the action of ultra-violet light and atmospheric electrical discharges Ozone isa very reactive gas whose uptake depends on the availabilityof antioxidants in the lining fluids [17 18 52] The surface ofthe lung is covered with a thin layer of fluid that containsa range of antioxidants that appear to provide the first lineof defence against air pollutants Mudway et al [17] studiedthe interaction of ozone with antioxidants and found that thehierarchy toward ozone in human epithelial lining fluid wasascorbic acid followed by uric acid and then glutathione Wuand Meng [34] analysed the effects of sea buckthorn seed oilon the protection against sulphur dioxide inhalation Theyfound that buckthorn seed oil contributed antioxidant effectsFurthermore study by Zhao et al [33] revealed the protectiveeffect of salicylic acid and vitamin C on sulphur dioxide-induced lipid peroxidation in mice

Tobacco smoke is one of the most common air pollutantsand generates high amounts of various ROSRNS Cigarette-induced oxidative stress was found to be affected by theprotective effects of vitamin C glutathione and other antiox-idants mainly as quenchers of ROSRNS (Table 1) [36ndash41]

Kienast et al [54] demonstrated that alveolar macro-phages and peripheral blood mononuclear cells become acti-vated following exposure to nitrogen dioxide Several studieshave demonstrated that certain antioxidants might play abeneficial role in NO

119909

-induced toxicity Guth and Mavis [55]and Sevanian et al [56 80] examined the effect of vitaminE content on the lungs Furthermore a study by Bohm et al[62] revealed that dietary uptake of tomato lycopene protectshuman cells against nitrogen dioxide-mediated damage Thepossible influence of dietary antioxidants especially vitaminC on the increasing prevalence of asthma was explored byHatch [81]

Particulate matter can also cause oxidative stress viadirect generation of ROS from the surfaces of soluble com-pounds altering the function of mitochondria or reducingthe activity of nicotinamide adenine dinucleotide phosphate-oxidase inducing the activation of inflammatory cells to gen-erate ROS and RNS and mediating oxidative DNA damage[63 82] Antioxidants could also provide protection againstparticulate matter-induced toxicity Indeed lung lining fluidantioxidants (urate glutathione and ascorbate) were demon-strated to be effective in a study by Greenwell et al [83] Luoet al [70] detected an inhibitory effect of green tea extract onthe carcinogenesis induced by the combination of asbestosand benzo(a)pyrene in rats drinking 2 green tea extractthroughout their lives

Oxidative Medicine and Cellular Longevity 3

Table 1 Studies demonstrating increased oxidative stressdamage due to air pollutant exposure and the protective effects of antioxidants

Air pollutant Increased oxidative stress markers Study Antioxidants exerting aprotective effect Study

Oxygen (O2)

Superoxide and hydrogenperoxide generation Floyd (1995) [8]

Catalases glutathioneperoxidases andperoxiredoxins

Nordberg and Arner (2001)[9]

Hydroxyl radical (OH∙)

Forman and Boveris (1982)[10]Keyer and Imlay (1996) [11]Hutchinson (1985) [12]Ames (1983) [13]

Oxidative DNA lesions

Friedberg et al (1995) [14]Speakman et al (2003) [15]Shackelford et al (1999)[16]

Ozone (O3)

Antioxidant depletionMudway et al (1996) [17]Pryor (1992) [18]Cross et al (2002) [3]

Vitamins C and E andbeta-carotene

Grievink et al (1999 1997)[19 20]Samet et al (2001) [21]Menzel (1994) [22]Romieu et al (2002) [23]Romieu et al (1998) [24]

Protein oxidation Kelly and Mudway (2003)[5] Grievink et al (2000) [25]

Membrane oxidation Ballinger et al (2005) [26]Inflammation Menzel (1994) [22]

Sulphurdioxide (SO2)

TBARS Meng et al (2003) [27]Meng and Bai (2004) [28] Vitamin E Ergonul et al (2007) [29]

Etlik et al (1997) [30]Zhao et al (2009) [31] Vitamin C

Depletion of endogenousantioxidants

Etlik et al (1997 1995)[30 32]Zhao et al (2008) [33]

Salicylic acid and vitamin C Zhao et al (2009) [31]

Malondialdehyde Wu and Meng (2003) [34] GSH Langley-Evans et al (1996)[35]

Change in the glutathione redoxsystem Sea buckthorn seed oil Wu and Meng (2003) [34]

Cigarettesmoke

Decreased antioxidant capacity

Midgette et al (1993) [36]Banerjee et al (1998) [37]Bloomer (2007) [38]Aycicek et al (2005) [39]Tsuchiya et al (2002) [40]Zhou et al (2000) [41]

Vitamin CBanerjee et al (2008) [42]Mayne and Cartmel (1999)[43]

Cruciferous vegetables andgreen tea((minus)-epigallocatechingallate (EGCG) andcaffeine)

Chung et al (1993) [44]Xu et al (1992) [45]

Lipid peroxidation Banerjee et al (1998) [37]Jha et al (2007) [46] Black tea Chung (1999) [47]

Oxidation of purines Jha et al (2007) [46]8-OH-dGuo Xu et al (1992) [45]

Decreased antioxidant vitaminactivities

Zhou et al (1997) [48]Dietrich et al (2003) [49]Chavez et al (2007) [50]Bloomer (2007) [38]

Tomato-based juicevitamin E andbeta-carotene

Mayne and Cartmel (1999)[43]

Protein damage and inflammation Banerjee et al (2008) [42]

Malondialdehyde (MDA) Chavez et al (2007) [50]Polidori et al (2003) [51]


Table 1 Continued


Nitrogenoxides (NO

119909

)

Aldehydes hydrogen peroxideand reactive oxygen intermediates

Pryor and Church (1991)[52]Last et al (1994) [53]Kienast et al (1994) [54]

Vitamin E Guth and Mavis (1986) [55]Sevanian et al (1982) [56]

Depletion of antioxidants Kelly and Tetley (1997) [57]Kelly et al (1996) [58] Vitamin C Rietjens et al (1986) [59]

Mohsenin (1987) [60]

Lipid peroxidation Sevanian et al (1982) [56]Khopde et al (1998) [61] Lycopene Bohm et al (2001) [62]

Particulatematter (PM)

Direct generation of ROS Gonzalez-Flecha (2004)[63]

N-acetylcysteine anddeferoxamine Pinho et al (2005) [64]

Proinflammatory mediatorsreleased from PM-stimulatedmacrophages

Gonzalez-Flecha (2004)[63]

Oxidative DNA damageGonzalez-Flecha (2004)[63]Aganasur et al (2001) [65]

Inhibitory effects on oxidativestress-related enzymes Hatzis et al (2006) [66]

Thiobarbituric acid reactivesubstances protein carbonyls Possamai et al (2010) [67] vitamins C and E Possamai et al (2010) [67]

Asbestos

ROS formation (oxygen freeradicals)

Kamp et al (1992) [68]Walker et al (1992) [69] Green tea extract Luo et al (1995) [70]

Hydrogen peroxide hydroxylradical and superoxide anion

Lewczuk and Owczarek(1992) [71] SOD Fattman et al (2006) [72]

Activation of phagocytic cellsKamp et al (1992) [68]Hei et al (2006) [73]Walker et al (1992) [69]

Increased 8-isoprostane Pelclova et al (2008) [74]

8-Hydroxy-21015840-deoxyguanosine Marczynski et al (2000)[75]

As the diet is the main source of antioxidant micronutri-ents a plausible link now exists between the exposure to airpollution and the quality of food consumed

22 Radiation-Induced Oxidative Stress and Protection againstIt Ionising radiation consists of highly energetic particleswhich can generate ROS These ROS can either be generatedprimarily via radiolysis of water or they may be formed bysecondary reactions Extensive doses of ionizing radiationhave been shown to have a mutating effect for exampleSperati et al [84] concluded that indoor radioactivity appearsto affect the urinary excretion of 8-OHdG among femaleswho are estimated to exhibit a higher occupancy in thedwellings measured than males (Table 2) Many compoundshave been demonstrated to protect against cell injury causedby radiation-induced ROS formation One of these com-pounds is ebselen a selenoorganic compound [85] Anothercompound is N-acetylcysteine which reduces nitrosativedamage during radiotherapy [86] as well as oxidative dam-age [87] The radioprotective effects of quercetin and theethanolic extract of propolis in gamma-irradiated mice werealso detected [88] The radioprotective and radiosensitisingactivities of curcuminwere demonstrated in a study by Jagetia[89]

Aside from ionising radiation nonionising radiation alsocauses oxidative stress Magnetic fields can affect biological

systems by increasing the release of free radicals There areseveral studies that indicate a relationship between electro-magnetic fields ROS levels and OS to exert toxic effects onliving organisms [90] Because it is unlikely that electromag-netic fields can induce DNA damage directly due to their lowenergy levels most studies have examined their effects on thecell membrane general and specific gene expression levelsand signal transduction pathways [91] Musaev et al [92]indicated that decimetric microwaves exert oxidant effectsat a high intensity of irradiation (specific absorption rate of15mWkg) and antioxidant effects at a low intensity (specificabsorption rate of 5mWkg) (Table 2) The protective effectsof melatonin and caffeic acid phenethyl ester against retinaloxidative stress during the long-term use of mobile phoneswere reported [93] Jajte et al [94] concluded that melatoninprovides protection against DNA damage to rat lymphocytesAnother investigation revealed that Ginkgo biloba preventsmobile phone-induced oxidative stress [95] Guney et al[96] found that vitamins E and C reduce phone-inducedendometrial damage

Visible and UV light are insufficient to ionize mostbiomolecules Nevertheless human exposure to ultravioletradiation has important public health implications Althoughthe skin possesses extremely efficient antioxidant activitiesduring aging theROS levels rise and the antioxidant activitiesdecline In addition UV exposure to the skin results in


Table2Stud

iesd

emon

stratin

gincreasedoxidatives

tressdam

aged

ueto

ionisin

gandno

nion

ising

radiationexpo

sure

andthep

rotectivee

ffectso

fantioxidants

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

Ionisin

gradiation

8-OHdG

Speratietal(19

99)[84]

Ebselen

TakandPark

(200

9)[85]

ROSsuperoxide

(O2

∙minus

)and

the

hydroxylradical(OH∙

)N-acetylcysteine

Kilciksiz

etal(20082011)

[8687]

DNAdamagea

ndlip

idmem

brane

damage

Quercetin

andthee

thanolicextracto

fprop

olis

Benk

ovicetal(2009)[88]

L-seleno

methion

inevitamin

Cvitamin

Esuccinatethec

ombinatio

nof

alph

a-lip

oica

cidandN-acetylcysteine

Wam

bietal(2009)[97]

And

rade

etal(2011)[98]

Curcum

inJagetia

(2007)

[89]

Sesamol

GG

Naira

ndC

KK

Nair

(2010)

[99]

Melaton

invitamin

E

El-M

issiry

etal(2007)[100]

Karbow

nikandRe

iter(2000)

[101]

Lycopene

Naire

tal(2003)

[102]

Noaman

etal(2002)[103]

Berbee

etal(200

9)[104]

Green

teap

olypheno

lsSrinivasan

etal(2009)[105]

Huetal(2011)[106]

Non

ionisin

gradiation

ROSprod

uctio

nKo

vacica

ndSomanathan(2010)

[90]

Alpha-to

coph

erol

Wolfetal(2005)

[107]

Simko

andMattss

on(200

4)[91]

N-acetyl-L

-cysteinea

ndepigallocatechin-3-gallate

Guler

etal(2008)[108]

Ozgur

etal(2010)[109]

Musaevetal(2004)[92]

Enhanced

lipid

peroxidatio

nand

alteredantio

xidant

defences

ystems

Simko

(2007)

[110]

Mela

toninandcaffeicacid

phenethyl

ester

Ozgun

eretal(2006)[93]

Jajte

etal(2001)[94]

Reiter(1994)[111]

DNAdamage

Jajte

etal(2001)[94]

Ginkgo

biloba

Ilhan

etal(2004

)[95]

L-carnitine

andselenium

Naziro

gluandGum

ral(2009)

[112]

VitaminsE

andC

Gun

eyetal(2007)

[96]


Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2

singletoxygenperoxyradicals

superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]

Photochemicaldamagetocellu

lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno

idsbeta-carotenemixture

oflutein

andlycopene

Heinrichetal(2003)[131]

Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]


the generation of ROS [118] such as singlet oxygen per-oxy radicals the superoxide anion and hydroxyl radicalswhich damage DNA and non-DNA cellular targets [113ndash116]and accelerate the skin aging process UV-radiation altersendogenous antioxidant protection for example in a studyby Shindo et al [127] after UV-irradiation the epidermaland dermal catalase and superoxide dismutase activities weregreatly decreased With respect to the protective role ofantioxidants many studies (Table 2) investigated the effect ofvitamin C on ultraviolet-radiation- (UVR-) induced damageOral vitamin C supplements resulted in significant increasesin plasma and skin vitamin C content [118] In the studyby Aust et al [134] the photoprotective effects of syntheticlycopene after 12 weeks of supplementation were examinedand significant increases in the lycopene serum and totalskin carotenoid levels were detected Studies of animals andhumans suggested that green tea polyphenols are photopro-tective and can be administered to prevent solar UVB light-induced skin disorders [137] A review of the research revealsthat polyphenols or other phytochemicals such as greentea polyphenols grape seed proanthocyanidins resveratrolsilymarin genistein and others exert substantial photo-protective effects against UV-induced skin inflammationoxidative stress DNA damage and so forth

Presently we are exposed to various sources of radiationboth ionising and nonionising The results of many studiesindicate that the human body can cope with radiation-induced oxidative stress to a certain degree by consuming anappropriate antioxidant diet

23 Pesticide-Induced Oxidative Stress and Protection againstIt Pesticides have become an integral constituent of theecosystem due to their widespread use distribution andthe stability of some of the pesticides in the environmentPesticide exposure may play a major role in increasedoxidative stress of the organisms and may result in altereddisease susceptibility Bagchi et al [145] demonstrated thatpesticides induce the production of ROS and oxidativedamage to tissues de Liz Oliveira Cavalli [146] found thatexposure to glyphosate causes oxidative stress and activatesmultiple stress-response pathways leading to Sertoli celldeath in prepubertal rat testis The role of oxidative stressin immune cell toxicity induced by the pesticides lindanemalathion and permethrin was examined by Olgun andMisra [147] Hassoun et al [148] reported that chlordaneproduces oxidative tissue damage based on the levels ofhepatic lipid peroxidation and DNA damage (Table 3) Buset al [149] reported that paraquat pulmonary toxicity resultsfrom the cyclic reduction and oxidation of paraquat Theresults of a study performed by Perez-Maldonado et al[150] demonstrated the induction of apoptosis by DDTHassoun et al [148] reported that lindane DDT chlor-dane and endrin exposure resulted in significant increasesin hepatic lipid peroxidation and DNA damage Anotherstudy by Senft et al [151] found out that dioxin increasesmitochondrial respiration-dependent ROS production Onthe other hand Ciftci et al [152] reported a protective effectof curcumin on the immune system of rats intoxicated with

2378-tetrachlorodibenzo-p-dioxin Additionally Hung etal [153] suggested that tea melanin might be a potentialagent against the development of tetrachlorodibenzodioxin-induced oxidative stress Gultekin et al [154] examined theeffects of melatonin and vitamins E and C on the reductionof chlorpyrifos-ethyl

Another group of pesticides are polychlorinated biphen-yls (PCBs) which also induce increased intracellular ROSproduction Zhu et al [155] indicated that different PCB com-pounds (Aroclor 1254 PCB153 and the 2-(4-chlorophenyl)-14-benzoquinone metabolite of PCB3) increase the steady-state levels of intracellular O

2

∙minus and H2

O2

in breast andprostate epithelial cells Many antioxidants showed protec-tion also against PCB-induced oxidative stress and damageRamadass et al [156] tested the hypothesis that flavonoidsmodify PCB-mediated cytotoxicity and found that flavonoidsinhibit PCB-induced oxidative stress Zhu et al [155] demon-strated that treatment with N-acetylcysteine significantlyprotected cells against PCB-mediated toxicity Red ginsengwhich displays a variety of biological and pharmacologicalactivities including antioxidant anti-inflammatory antimu-tagenic and anticarcinogenic effects was found to protectthe body against oxidative stressdamage induced by PCBexposure [157] Sridevi et al [158] also reported that theeffect of alpha-tocopherol against PCB-inducedneurotoxicityresulted in decreased oxidative stress Another study reportedthe synergistic effects of vitamins C and E against PCB-(Aroclor 1254) induced oxidative damage [159]

Dioxins and furans are byproducts of chemicals pro-duction Dioxins may be released into the environmentthrough the production of pesticides and other chlorinatedsubstances Both dioxins and furans are related to a varietyof incineration reactions and the use of a variety of chemicalproducts Ciftci and coworkers reported that dioxin (2378-tetrachlorodibenzo-p-dioxin TCDD) causes an oxidativestress response in the rats liver The subcellular sources andunderlying mechanisms of dioxin-induced reactive oxygenspecies however are not well understood TCDD increasesthe formation of thiobarbituric acid-reactive substances Italso causes a significant decline in the levels of glutathionecatalase GSH-Px and Cu-Zn superoxide dismutase in rats[160] The impact of 2-furan-2-yl-1H-benzimidazole on vita-mins A E C and Se malondialdehyde and glutathioneperoxidase levels on rats was analysed in a study by Karataset al [161] The results showed that vitamins A E C andSe levels were lower than the control groups while serumMDA level andGSH-Px activity flexibly increased dependingon the injection days The observed decreases in vitamins AE C and Se levels in the blood might be causally relatedto the increased amount of ROS The potential protectiveeffect of quercetin on TCDD induced testicular damage inrats was studied by Ciftci et al [160] The results showed thatexposure to TCDD induces testicular damage and quercetinprevents TCDD-induced testicular damage in rats Resver-atrolrsquos antioxidative effects were also investigated against ina study by Ishida et al [162] The results suggested that oralresveratrol is an attractive candidate for combating dioxintoxicity Turkez et al [163] analysed effects of propolis againstTCDD induced hepatotoxicity in rats and found that propolis


Table 3 Studies demonstrating increased oxidative stressdamage due to pesticide exposure and the protective effects of antioxidants

Pesticide Increased oxidative stressmarkers Study Antioxidants exerting a

protective effect Study

General

ROSBagchi et al (1995) [145]Song et al (2007) [164]Olgun and Misra (2006) [147]

DNA damageBagchi et al (1995 1996)[145 165]Kisby et al (2009) [166]

Alterations in antioxidantenzymes and the glutathioneredox system

Yi et al (2007) [167]

Increased level ofmalondialdehydeLipid peroxidation

Kesavachandran et al (2006)[168]Hassoun et al (1993) [148]

Bipyridyliumherbicides(paraquat diquatand difenzoquat)

Production of superoxide anionsand singlet oxygen Bus et al (1976) [149] Selenium

Combs and Peterson (1983)[169]Glass et al (1985) [170]Cheng et al (1998) [171]

Lipid peroxidation (peroxidationof cellular membranes) Bus et al (1976) [149]


Takizawa et al (2007) [172]Glutathione reductaseand superoxidedismutase

Aono et al (1995) [173]

Organo-phosphateinsecticides

Lipid peroxidationGultekin et al (2001) [154]Akturk et al (2006) [174]Hassoun et al (1993) [148]

Melatonin vitamin Cand vitamin E Gultekin et al (2001) [154]

Decreased antioxidant defenceGultekin et al (2001) [154]Verma et al (2007) [175]Akturk et al (2006) [174]

Vitamins A E and CVerma et al (2007) [175]Altunas et al (2002) [176]Akturk et al (2006) [174]

Increased ROS production Bagchi et al (1995) [145]DNA damage Bagchi et al (1995) [145] Zinc Goel et al (2005) [177]

Aldrin anddieldrin

ROS production Stevenson et al (1999) [178] Alpha-tocopherol andascorbic acid

Bachowski et al (1998)[179]Stevenson et al (1995) [180]

Depletion of the antioxidantdefence Klaunig et al (1995) [181]

Lipid peroxidation Bachowski et al (1998) [179]Klaunig et al (1995) [181]

DNA damage Klaunig et al (1995) [181]

DDTROS production Perez-Maldonado et al (2005)

[150] N-acetyl-L-cysteine Perez-Maldonado et al(2005) [150]

Lipid peroxidation Hassoun et al (1993) [148]DNA damage Hassoun et al (1993) [148]

Polychlorinateddibenzo-para-dioxins (dioxins)andpolychlorinateddibenzo furans(furans)

Depletion of the antioxidantdefence

Ciftci et al (2011) [160]Stohs (1990) [182]Karatas et al (2008) [161]

Quercetin Ciftci et al (2011) [160]

Lipid peroxidation Stohs (1990) [182]Karatas et al (2008) [161]

Curcumin 120573-myrceneand 18-cineole

Ciftci et al (2011) [160]Ciftci et al (2010) [152]

Resveratrol Ishida et al (2009) [162]Tea melanin Hung et al (2006) [153]

TBARS Ciftci et al (2011) [160] Vitamin A and vitamin E Alsharif and Hassoun(2004) [183]

Increased ROS production Senft et al (2002) [151]8-OHdG Wen et al (2008) [184]DNA damage Stohs (1990) [182]


Table 3 Continued



Polychlorinatedbiphenyls (PCBs)

ROS production (superoxide andhydrogen peroxide)

Song et al (2008) [185]Zhu et al (2009) [155]

Dietary flavonoids(epigallocatechin-3-gallate (EGCG) andquercetin)

Ramadass et al (2003) [156]

Imbalance in the antioxidantstatus

Zhu et al (2009) [155]Shimizu et al (2007b) [186]

N-acetylcysteine (NAC)and the combination ofpolyethylene glycol(PEG)-conjugatedCuZn-SOD andPEG-conjugated catalase

Zhu et al (2009) [155]

Lipid peroxidation Shimizu et al (2007a) [187] Red ginseng Park et al (2010) [157]

Alpha-tocopherol Banudevi et al (2006) [188]Sridevi et al (2007) [158]

Alpha-tocopherol andascorbic acid

Krishnamoorthy et al(2007) [189]Murugesan et al (2005)[159]Zhou and Zhang (2005)[190]

Melatonin Venkataraman et al (2008)[191]

Lycopene Elumalai et al (2009) [192]

alleviate pathological effects and prevents the suppression ofantioxidant enzymes in the livers

It can be concluded that the stimulation of ROS pro-duction the induction of lipid peroxidation and oxidativeDNA and protein damage and the disturbance of the totalantioxidant capacity of the body are mechanisms of thetoxicity induced by most pesticides including organophos-phates bipyridyl herbicides and organochlorines Antioxi-dant nutrients and related bioactive compounds common infruits and vegetables as well as food additives can protectagainst environmental exposure to pesticides-induced oxida-tive stressdamage (Table 3)

24 Household Chemical-Induced Oxidative Stress and Protec-tion against It Thepredominant use of industrial resins suchas urea-formaldehyde phenol-formaldehyde polyacetal andmelamine-formaldehyde resins can be found in domesticenvironments in adhesives and binders for wood productspulp products paper products plastics synthetic fibres andin textile finishing Formaldehyde was demonstrated to exertincreased oxidative stress formation (Table 4) primarily aslipid peroxidation as found in a study performed by ChangandXu [193] Also in the case of household chemical-inducedoxidative stress certain antioxidants showed protection In arecent study Kose et al [194] reported that rose oil inhalationprotects against formaldehyde-induced testicular damage inrats Zararsiz et al [195] demonstrated that exposure toformaldehyde increased the free radical levels in rats andthat omega-3 fatty acids prevented this oxidative stress Theprotective effect of melatonin against formaldehyde-inducedrenal oxidative damage in rats has also been reported [196]

Many studies have been performed on carbon tetrachlo-ride because it is a well-known model of inducing chemicalhepatic injury in mice Also carbon tetrachloride exposureincreases oxidative stressdamage in tested model organismsand carbon tetrachloride-induced damage has been reversedby many antioxidants examined Thus the antioxidant andhepatoprotective effects of many antioxidants and plantextracts against oxidative stress induced by carbon tetra-chloride have been reported [198] For example chlorella-mediated protection against carbon tetrachloride-inducedoxidative damage in rats was demonstrated in a study byPeng et al [224] Ozturk et al [201] found that apricot(Prunus armeniaca L) feeding exerted beneficial effects Thepotency of vitamin E to enhance the recovery from carbontetrachloride-induced renal oxidative damage in mice wasrevealed in a study byAdaramoye [202]The protective effectsof Curcuma longa Linnwere reported by Lee et al [205] Theprotective effect of blackberry extract against oxidative stressin carbon tetrachloride-treated rats was reported by Cho etal [207]

Chemicals found in common household and personalcare goods are major sources of oxidant exposure that canlead to oxidative stress Many antioxidants such as mela-tonin vitamin E ascorbate and extracts from various plantsfor example rose green tea and blackberry were reported todecrease oxidative stress andor damage in vivo and in vitro

25 Disinfection Byproducts (DBP) and Other Water BornPollutants The beneficial role of water ingestion can beminimised due to the formation of disinfection byproductsChlorination and ozonation in the water treatment process


Table 4 Studies demonstrating increased oxidative stressdamage due to exposure to selected toxic compounds and the protective effects ofantioxidants

Other Increased oxidative stressmarkers Study Antioxidants exerting a


FormaldehydeLipid peroxidation Chang and Xu (2006) [193] Rose oil Kose et al (2011) [194]Imbalance in antioxidantstatus Chang and Xu (2006) [193] Melatonin Zararsiz et al (2007) [196]

Carbontetrachloride(CCl4)

Increased ROS production Brent and Rumack (1993) [197] Electrolysed reduced water Tsai et al (2009) [198]

Lipid peroxidation Morrow et al (1992) [199]Basu (2003) [200]

Apricot(Prunus armeniaca L) Ozturk et al (2009) [201]

Vitamin E Adaramoye (2009) [202]Megahydrate silica hydrideLutein

Hsu et al (2010) [203]Sindhu et al (2010) [204]

Curcuma longa Lee et al (2010) [205]

Acetyl-L-carnitine Annadurai et al (2011)[206]

Blackberry extract Cho et al (2011) [207]Capsaicin Hassan et al (2012) [208]Propolis Bhadauria (2012) [209]Melatonin and pinoline Aranda et al (2010) [210]Black and green tea Almurshed (2006) [211]

Water disinfectionbyproducts

ROS production(OH∙ H2O2 and singletO2)

Hassoun and Ray (2003) [212] Ascorbate glutathione andurate Yadav et al (2010) [213]

Ascorbate and desferalN-acetyl-cysteine

Yadav et al (2010) [213]Leustik et al (2008) [214]

Ascorbate and deferoxamine Zarogiannis et al (2011)[215]

Green tea catechins Kawai et al (2008) [216]Melatonin Tan et al (2000) [217]

S-allylcysteine Medina-Campos et al(2007) [218]

Thioallyl compounds fromgarlic

Arguello-Garcıa et al(2010) [219]

Trolox Strosova et al (2009) [220]Vitamin C Carr et al (2000) [221]Glutathione Rezk et al (2004) [222]Many other localMediterranean plant foods Schaffer et al (2004) [223]

are believed to produce various active oxygen species whichseem to participate in the reactionwith fumic acid pollutantsand bacteria (Table 4) Hypochlorous acid (HOCl) is formedwhen Cl

2

is added to the water for disinfection purposesThis acid is highly reactive and is capable of oxidising manybiological molecules HOCl reacts with O

2

minus to give OH∙ andwith H

2

O2

to form singlet O2

HOCl affects endogenousenzymatic antioxidants and increases oxidative stress Forexample Hassoun and Ray [212] demonstrated the inductionof oxidative stress and cellular death of drinking waterdisinfection byproducts Similar observations were reportedby Leustik et al [214] Studies suggest that Cl

2

inhalationdamages both airway and alveolar epithelial tissues and thatthese damaging effects were ameliorated by the prophylacticadministration of low molecular-weight antioxidants Trolox

was reported to be protective against oxidative injury inducedby HOCl to Ca-ATPase in the sarcoplasmic reticulum ofskeletal muscle [220] Ascorbic acid might also play a pro-tective role (Table 4) especially in individuals consumingsupplements containing this vitamin Also thioallyl and S-allylcysteine (both are garlic-derived compounds) melato-nine glutathione glutathione disulfide S-methylglutathionelipoic acid and dihydrolipoic acid were reported to protectagainst hypochlorous acid and peroxynitrite-induced dam-age [217ndash219 222])

Additionally the following plant extracts display a protec-tive effect against HOCl-induced oxidative damage Agaricuscampestris Cynara cardunculus Thymus pulegioides andVicia faba [223] When resolving the problem of DBP firstthe cause of their formation should be assessed with different


engineering approaches DBP for example by moving thepoint of chlorination downstream in the treatment trainreducing the natural organic matter precursor concentrationreplacing prechlorination by peroxidation and so forth

The use of antioxidants as compounds which ameliorateDBP-induced toxicity should be just the last alternative whenall other approaches deal with the DBP formation in thedrinking water fail

Researches in the past two decades have pointed out thatredox active metals like iron (Fe) copper (Cu) chromium(Cr) cobalt (Co) and other metals present in water possessthe ability to produce ROS such as superoxide anion radicaland nitric oxide Disruption of metal ion homeostasis maylead to oxidative stress a state where increased formationof reactive oxygen species overwhelms body antioxidantprotection and subsequently induces DNA damage lipidperoxidation protein modification and other effects [225]Pollutants in water like heavy metals As Cd Cu FePb and Zn can cause oxidative stress in fish [226] Onother hand Yang and coworkers [227] reports that waterspinach containing chlorophyll and lycopene have potentialto reduce cytotoxicity and oxidative stress in liver inducedby heavy metals Besides heavy metals also pesticides inwater can represent sources of oxidative stress Atrazineand chlorpyrifos are the most common pesticides found infreshwater ecosystems throughout the world Xing et al [228]investigated the oxidative stress responses in the liver ofcommon carp after exposure to atrazine and chlorpyrifos andfound that exposure or theirmixture could induce decrease inantioxidant enzyme activities and increase in MDA contentin a dose-dependent manner Eroglu et al [229] reportedorganophosphate pesticides produce oxidative stress due tothe generation of free radicals which alter the antioxidantdefence system in erythrocytes and that vitamins C and E canact as protective role

26 The Role of Oxidative Stress in Noise-Induced HearingDamage Noise is a disturbing and unwanted sound Expo-sure to noise causes many health problems such as hearingloss sleep disturbance and impairs performance as well aseffecting cognitive performance It also increases aggressionand reduces the processing of social cues seen as irrelevant totask performance as well as leading to coronary heart diseasehypertension higher blood pressure increased mortalityrisk serious psychological effects headache anxiety andnausea ([230] and references within) Prolonged exposure tonoise can also cause oxidative stress in the cochlea whichresults in the loss (via apoptotic pathways) of the outer haircells of the organ of Corti Increased noise exposure results inincreased levels of reactive oxygen species formation that playa significant role in noise-induced hair cell death [231] Acuteas well as long-term exposure to noise can produce excessivefree radicals alter endogenous antioxidative enzymes assuperoxide dismutase catalase and glutathione peroxidase[232 233]

In a study by Demirel et al [230] the effect of noise onoxidative stress parameters in rats was analyzed bymeasuring

malondialdehyde nitric oxide levels and glutathione per-oxidase activity The results showed an elevation in MDAlevel an indicator of lipid peroxidation as well as NO leveland GSH-Px activity through noise exposure suggesting thatthe presence of oxidative stress may have led to variousdegrees of damages in the cells Additionally increases inoxidative stress parameters such asMDA level and decreasesin CAT and SOD activities in textile workers exposed toelevated levels of noise supports the hypothesis that noisecauses oxidative stress [234] It seems that noise might causedamage not only in the ears but also across the entirebody leading to oxidative stress [230] In a study by vanCampen et al [235] the time course of ROSdamage followingexposure was assessed Based upon oxidative DNA damagepresent in the cochlea following intense noise the researcherspostulate that the first 8 h following exposure might be acritical period for antioxidant treatment Thus the ROSquenching properties of antioxidants and medicinal plantsare attracting more and more research to counteract noise-induced oxidative stress Manikandan and Devi [232] inves-tigated the antioxidant property of alpha-asarone againstnoise stress induced changes in different regions of the ratbrain and their data proved that the antioxidant propertyof alpha-asarone acts against noise stress induced damageThe aim of a study performed by Manikandan et al [233]was to evaluate the protective effect of both ethyl acetateandmethanolic extract ofAcorus calamus against noise stressinduced changes in the rat brain Both the ethyl acetateand methanolic extract of Acorus calamus protected mostof the changes in the rat brain induced by noise stress N-acetyl-cysteine also offered protection against noise-inducedhearing loss in the Sprague Dawley rat [236] The studyby Ewert et al [237] determined if administration of acombination of antioxidants 24-disulfonyl 120572-phenyl tertiarybutyl nitrone (HPN-07) and N-acetylcysteine could reduceboth temporary and permanent hearing loss The resultsshowed that a combination of antioxidantsHPN-07 andNACcan both enhance the temporary threshold shift recovery andprevent permanent threshold shift by reducing damage to themechanical and neural components of the auditory systemwhen administered shortly after blast exposure Additionallyarboxy alkyl esters (esters of quinic acid found in fruits andvegetables) have been shown to improve DNA repair capacityof spiral ganglion neurons in response to noise stress [238]

The problem of oxidative stress in the production ofhearing loss is even worse when the synergistic effects takesplace since a broad range of environmental and occupationalcontaminants can interact with noise to enhance noise-induced hearing loss for example through carbonmonoxideand by acrylonitrile [239]

27 Adverse or Insignificant Effects of Antioxidant Treatmentafter Exposure to Environmental Pollutants Administrationof antioxidants in cases of environmentally induced oxidativestress does not always demonstrate protection (Table 5)Hackney et al [240] analysed whether vitamin E supplemen-tation protected againstO

3

exposure and found no significantdifferences between the vitamin E- and placebo-treated


Table 5 Studies demonstrating adverse or insignificant effects of antioxidant treatment after exposure to environmental pollutants

Environmental pollutant Antioxidants displaying adverse orinsignificant effects Study

Ozone (O3) Vitamin E Hackney et al (1981) [240]

Cigarette smoke Beta-carotene (synthetic)Ruano-Ravina et al (2006) [241]Albanes (1999) [242]Neuhouser et al (2003) [243]

Asbestos Beta-carotene van Helden et al (2009) [244]

UVR

Beta-carotene Stahl et al (2006) [124]

Vitamin E and beta-carotene (noprotective effect)

McArdle et al (2004) [245]Wolf et al (1988) [246]Garmyn et al (1995) [247]

Bipyridinium herbicides (paraquatdiquat and difenzoquat) Iron and copper Korbashi et al (1986) [248]

Kohen and Chevion (1985) [249]Polychlorinated dibenzo-para-dioxins(dioxins) and polychlorinateddibenzofurans (furans)

Vitamin E (no protective effect) Latchoumycandane and Mathur (2002)[250]

No extraexposure to environmentalpollutants

Green tea catechins (enhanced coloncarcinogenesis in rats) Furukawa et al (2003) [251]

Melatonin (may exhibit carcinogenicpotential) Sakano et al (2004) [252]

groups Another study demonstrated that in a high-riskgroup such as smokers high doses of beta-carotene increasedthe rate of lung cancer [241] Additionally the results oflarge controlled trials of an intervention of beta-carotenesupplementation did not support the detected beneficialassociations or a role for supplemental beta-carotene in lungcancer prevention instead they provided striking evidencefor its adverse effects among smokers [242] McArdle et al[118] investigated the effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-inducedoxidative stress to the human skin The results revealed thatvitamin E or beta-carotene supplementation displayed noeffect on the sensitivity of the skin to UVR A study byStahl et al [122] was performed in which the antioxidanteffect of carotenoids and tocopherols was investigated basedon their ability to scavenge ROS generated during photoox-idative stress The antioxidants used in this study providedprotection against erythema in humans andmay be useful fordiminishing the sensitivity to ultraviolet light (Table 5)

Iron and copper have been reported to aggravate thetoxicity of paraquat in E coli Treatment with ferrous ironin a study by Korbashi et al [248] led to an enhancementof bacterial killing by paraquat whereas treatment withchelating agents such as nitrilotriacetate and desferriox-amine markedly reduced up to complete abolishment thetoxic effects Some compounds contribute to the antioxidantdefence by chelating transition metals and preventing themfrom catalysing the production of free radicals in the cellMetal-chelating antioxidants such as transferrin albuminand ceruloplasmin ameliorate radical production by inhibit-ing the Fenton reaction which is catalysed by copper or ironLatchoumycandane and Mathur [250] investigated whethertreatment with vitamin E protects the rat testis against oxida-tive stress induced by tetrachlorodibenzodioxin and revealed

that the activities of antioxidant enzymes and the levels ofhydrogen peroxide and lipid peroxidation did not changein the animals coadministered tetrachlorodibenzodioxin andvitamin E Although several studies have demonstrated theprotective effect of antioxidant administration against oxida-tive stress it is important to note that not all antioxidantsexert health benefits

28 What Could Be the Reason The inappropriate useof dietary supplements may lead to ldquoantioxidative stressrdquoDetailed description of the negative effects of antioxidantscan be found in publications by Poljsak et al [253] PoljsakandMilisav [254] and references therein Briefly the intake ofonly one antioxidantmay alter the complex systemof endoge-nous antioxidative defence of cells or alter the cell apoptosispathways [255] The beneficial physiological cellular use ofROS is being demonstrated in different fields includingintracellular signalling and redox regulation and syntheticantioxidants cannot distinguish among the radicals that havea beneficial role and those that cause oxidative damage tobiomolecules If administration of antioxidant supplementsdecreases total ROSRNS formation itmay also interferewiththe immune system to fight bacteria and essential defensivemechanisms for removal of damaged cells including thosethat are precancerous and cancerous [256] When largeamounts of antioxidant nutrients are taken they can also actas prooxidants by increasing oxidative stress [257 258] Noneof the major clinical studies using mortality or morbidity asan end point has found positive effects of antioxidant suchas vitamin C vitamin E or 120573-carotene supplementationSome recent studies demonstrated that antioxidant therapydisplays no effect and can even increasemortality (TheAlpha-Tocopherol Beta-Carotene Cancer Prevention Study Group1994 [259ndash261] Heart Protection StudyCollaborativeGroup


2002 Age-Related Eye Disease Study Research Group 2001)On the other hand antioxidant supplements do appear to beeffective in lowering an individualrsquos oxidative stress if hisherinitial oxidative stress is above normal or above hisherset point of regulation [262 263] Thus the antioxidantsupplements may help the organism to correct the elevatedlevels of oxidative stress when it cannot be controlled by theendogenous antioxidants

3 Conclusions

There is substantial evidence that environmental pollutionincreases oxidative stress [264] and that dietary antioxidantsupplementation andor increased ingestion of fruit andvegetable may play a role in neutralising or buffering theeffects of pollutants that display oxidising properties Invitro and in vivo studies suggest that antioxidant nutrientsand related bioactive compounds common in fruits andvegetables can protect against environmental toxic insultsIt is important to emphasise that antioxidants as dietarysupplements can provide protection against ROS-induceddamage under conditions of elevated oxidative stress to theorganism It could be postulated that antioxidants wouldbe therapeutically effective under circumstances of elevatedoxidative stress or in aged mammals exposed to a stressorthat generates exacerbated oxidative injury Evidence is pre-sented demonstrating that synthetic antioxidant supplementscannot provide appropriate or complete protection againstoxidative stress and damage under ldquonormalrdquo conditions andthat the administration of antioxidants to prevent diseaseor the aging process is controversial under conditions ofldquonormalrdquo oxidative stress Many clinical trials in whichindividuals received one ormore synthetic antioxidants failedto detect beneficial effects (reviewed in [253]) Thus theresults of clinical trials of exogenous antioxidant intakeare conflicting and contradictory These findings indicatethat other compounds in fruits and vegetables (possiblyflavonoids) or a complex combination of compounds maycontribute to the improvement in cardiovascular health andthe decrease in cancer incidence detected among individualswho consume more of these foods [265 266]

It must be understood that the use of synthetic vitaminsupplements is not an alternative to regular consumptionof fruits and vegetables Cutler explains that most humansmaintain stable levels of oxidative stress and no matter howmuch additional antioxidant that individuals consume intheir diet no further decrease in oxidative stress occursHowever antioxidant supplements do appear to be effectivein lowering an individualrsquos oxidative stress if hisher initialoxidative stress level is above normal or above hisher stablyregulated level [262 263]Thus antioxidant supplementsmayonly provide a benefit to an organism if it was necessaryto correct a high level of oxidative stress that could not becontrolled by endogenous antioxidants All of this evidenceindicates the need to determine an individualrsquos oxidativestress level prior to the initiation of antioxidant supplementtherapy Both the ROSRNS formation and the antioxidativedefense potential should be measured in a person in order to

determine hisher oxidative stress statusMultiplemethods ofoxidative stress measurement are available today each withtheir own advantages and disadvantages (reviewed in [253])

In the end it should be stressed that more researchshould be performed to strengthen the evidence for dietarysupplements as modulators of the adverse effects caused byincreased exposure to environmental pollution

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

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[2] A Valavanidis T VlahogianniMDassenakis andM ScoullosldquoMolecular biomarkers of oxidative stress in aquatic organismsin relation to toxic environmental pollutantsrdquoEcotoxicology andEnvironmental Safety vol 64 no 2 pp 178ndash189 2006

[3] C E Cross G Valacchi B Schock et al ldquoEnvironmental oxi-dant pollutant effects on biologic systems a focus on micronu-trient antioxidant-oxidant interactionsrdquo American Journal ofRespiratory and Critical Care Medicine vol 166 supplement 1pp S44ndashS50 2002

[4] B Brunekreef and S T Holgate ldquoAir pollution and healthrdquoTheLancet vol 360 no 9341 pp 1233ndash1242 2002

[5] F J Kelly and I S Mudway ldquoProtein oxidation at the air-lunginterfacerdquo Amino Acids vol 25 no 3-4 pp 375ndash396 2003

[6] ANel ldquoAir pollution-related illness effects of particlesrdquo Sciencevol 308 no 5723 pp 804ndash806 2005

[7] R B Schlesinger N Kunzli G M Hidy T Gotschi and MJerrett ldquoThe health relevance of ambient particulate mattercharacteristics Coherence of toxicological and epidemiologicalinferencesrdquo Inhalation Toxicology vol 18 no 2 pp 95ndash1252006

[8] R A Floyd ldquoMeasurement of oxidative stress in vivordquo in TheOxygen Paradox pp 89ndash103 Cleup University Press PadovaItaly 1995

[9] J Nordberg and E S J Arner ldquoReactive oxygen speciesantioxidants and the mammalian thioredoxin systemrdquo FreeRadical Biology andMedicine vol 31 no 11 pp 1287ndash1312 2001

[10] H J Forman and A Boveris ldquoSuperoxide radical and hydrogenperoxide in mitochondriardquo in Free Radicals in Biology E PryorEd pp 65ndash90 Academic Press New York NY USA 1982

[11] K Keyer and J A Imlay ldquoSuperoxide accelerates DNA dam-age by elevating free-iron levelsrdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 93 no24 pp 13635ndash13640 1996

[12] F Hutchinson ldquoChemical changes induced in DNA by ionizingradiationrdquo Progress in Nucleic Acid Research and MolecularBiology vol 32 pp 115ndash154 1985

[13] B N Ames ldquoDietary carcinogens and anticarcinogensrdquo Sciencevol 221 no 4617 pp 1256ndash1263 1983

[14] E C Friedberg L D McDaniel and R A SchultzDNA Repairand Mutagenesis ASM Press Washington DC USA 1995

[15] J R Speakman A van Acker and E J Herper ldquoAge-relatedchanges in the metabolism and body composition of three dogbreeds and their relationship to life expectancyrdquo Aging Cell vol2 no 5 pp 265ndash275 2003


[16] R E Shackelford W K Kaufmann and R S Paules ldquoCellcycle control checkpoint mechanisms and genotoxic stressrdquoEnvironmental Health Perspectives vol 107 no 1 pp 5ndash24 1999

[17] I S Mudway D Housley R Eccles et al ldquoDifferential depletionof human respiratory tract antioxidants in response to ozonechallengerdquo Free Radical Research vol 25 no 6 pp 499ndash5131996

[18] W A Pryor ldquoHow far does ozone penetrate into the pulmonaryairtissue boundary before it reactsrdquo Free Radical Biology andMedicine vol 12 no 1 pp 83ndash88 1992

[19] L Grievink A G Zijlstra and X Ke ldquoDouble-blind interven-tion trial onmodulation of ozone effects onpulmonary functionby antioxidant supplementsrdquoAmerican Journal of Epidemiologyvol 149 no 4 pp 306ndash314 1999

[20] L Grievink A G Zijlstra X Ke and B Brunekreef ldquoAcuteeffects of ozone on pulmonary function in antioxidant supple-mented cyclistsrdquo European Respiratory Journal vol 10 supple-ment 25 article 229S 1997

[21] J M Samet G E Hatch D Horstman et al ldquoEffect ofantioxidant supplementation on ozone-induced lung injury inhuman subjectsrdquo American Journal of Respiratory and CriticalCare Medicine vol 164 no 5 pp 819ndash825 2001

[22] D B Menzel ldquoThe toxicity of air pollution in experimentalanimals and humans the role of oxidative stressrdquo ToxicologyLetters vol 72 no 1ndash3 pp 269ndash277 1994

[23] I Romieu J J Sienra-Monge M Ramırez-Aguilar et alldquoAntioxidant supplementation and lung functions among chil-dren with asthma exposed to high levels of air pollutantsrdquo TheAmerican Journal of Respiratory and Critical Care Medicine vol166 no 5 pp 703ndash709 2002

[24] I Romieu F Meneses M Ramirez et al ldquoAntioxidant supple-mentation and respiratory functions among workers exposedto high levels of ozonerdquo American Journal of Respiratory andCritical Care Medicine vol 158 no 1 pp 226ndash232 1998

[25] L Grievink H A Smit and B Brunekreef ldquoAnti-oxidants andair pollution in relation to indicators of asthma and COPD areview of the current evidencerdquoClinicalampExperimental Allergyvol 30 no 10 pp 1344ndash1354 2000

[26] C A Ballinger R Cueto G Squadrito et al ldquoAntioxidant-mediated augmentation of ozone-induced membrane oxida-tionrdquo Free Radical Biology and Medicine vol 38 no 4 pp 515ndash526 2005

[27] Z Meng G Qin B Zhang et al ldquoOxidative damage of sulfurdioxide inhalation on lungs and hearts of micerdquo EnvironmentalResearch vol 93 no 3 pp 285ndash292 2003

[28] Z Meng and W Bai ldquoOxidation damage of sulfur dioxide ontesticles of micerdquo Environmental Research vol 96 no 3 pp298ndash304 2004

[29] Z Ergonul A Erdem Z D Balkanci and K Kilinc ldquoVitamin Eprotects against lipid peroxidation due to cold-SO

2

coexposurein mouse lungrdquo Inhalation Toxicology vol 19 no 2 pp 161ndash1682007

[30] O Etlik A Tomur M Tuncer A Yalcin Ridvanagaoglu andO Andac ldquoProtective effect on antioxidant vitamins on redblood cell lipoperoxidation induced by SO2 inhalationrdquo Journalof Basic and Clinical Physiology and Pharmacology vol 8 no 1-2 pp 31ndash43 1997

[31] J Q Zhao Y F Wen M Bhadauria et al ldquoProtective effectsof propolis on inorganic mercury induced oxidative stress inmicerdquo Indian Journal of Experimental Biology vol 47 no 4 pp264ndash269 2009

[32] O Etlik A Tomur M N Kutman S Yorukan and O DumanldquoThe effects of sulfur dioxide inhalation and antioxidantvitamins on red blood cell lipoperoxidationrdquo EnvironmentalResearch vol 71 no 1 pp 25ndash28 1995

[33] H Zhao X Xu J Na et al ldquoProtective effects of salicylic acidand vitamin C on sulfur dioxide-induced lipid peroxidation inmicerdquo Inhalation Toxicology vol 20 no 9 pp 865ndash871 2008

[34] D Wu and Z Meng ldquoEffect of sulfur dioxide inhalation onthe glutathione redox system in mice and protective role of seabuckthorn seed oilrdquo Archives of Environmental Contaminationand Toxicology vol 45 no 3 pp 423ndash428 2003

[35] S C Langley-Evans G J Phillips and A A Jackson ldquoSulphurdioxide a potent glutathione depleting agentrdquo ComparativeBiochemistry and Physiology C Pharmacology Toxicology andEndocrinology vol 114 no 2 pp 89ndash98 1996

[36] A S Midgette J A Baron and T E Rohan ldquoDo cigarettesmokers have diets that increase their risks of coronary heartdisease and cancerrdquoAmerican Journal of Epidemiology vol 137no 5 pp 521ndash529 1993

[37] K K Banerjee P Marimuthu A Sarkar and R N ChaudhurildquoInfluence of cigarette smoking on Vitamin C glutathione andlipid peroxidation statusrdquo Indian Journal of Public Health vol42 no 1 pp 20ndash23 1998

[38] R J Bloomer ldquoDecreased blood antioxidant capacity andincreased lipid peroxidation in young cigarette smokers com-pared to nonsmokers impact of dietary intakerdquo NutritionJournal vol 6 article 39 2007

[39] A Aycicek O Erel and A Kocyigit ldquoDecreased total antioxi-dant capacity and increased oxidative stress in passive smokerinfants and their mothersrdquo Pediatrics International vol 47 no6 pp 635ndash639 2005

[40] M Tsuchiya A Asada E Kasahara E F Sato M Shindo andM Inoue ldquoSmoking a single cigarette rapidly reduces combinedconcentrations of nitrate and nitrite and concentrations ofantioxidants in plasmardquo Circulation vol 105 no 10 pp 1155ndash1157 2002

[41] J F Zhou X F Yan F Z Guo N Y Sun Z J Qian and D YDing ldquoEffects of cigarette smoking and smoking cessation onplasma constituents and enzyme activities related to oxidativestressrdquo Biomedical and Environmental Sciences vol 13 no 1 pp44ndash55 2000

[42] S Banerjee R Chattopadhyay A Ghosh et al ldquoCellularand molecular mechanisms of cigarette smoke-induced lungdamage and prevention by vitamin Crdquo Journal of Inflammationvol 5 article 21 2008

[43] S T Mayne and B Cartmel ldquoAntioxidant vitamin supplemen-tation and lipid peroxidation in smokersrdquo American Journal ofClinical Nutrition vol 69 no 6 Article ID 1292 1999

[44] F L Chung M A Morse K I Eklind Y Xu R RylanderandNKrinsky ldquoInhibition of the tobacco-specific nitrosamine-induced lung tumorigenesis by compounds derived from cru-ciferous vegetables and green teardquo Annals of the New YorkAcademy of Sciences vol 686 pp 186ndash201 1993

[45] Y Xu C T Ho S G Amin C Han and F L Chung ldquoInhibitionof tobacco-specific nitrosamine-induced lung tumorigenesis inAJ mice by green tea and its major polyphenol as antioxidantsrdquoCancer Research vol 52 no 14 pp 3875ndash3879 1992

[46] J C Jha B R Maharjan D Adhikari et al ldquoCigarette smokeinduced oxidative insult in local population of Pokharardquo Kath-manduUniversityMedical Journal vol 5 no 4 pp 511ndash517 2007

[47] F L Chung ldquoThe prevention of lung cancer induced by atobacco-specific carcinogen in rodents by green and black


teardquo Proceedings of the Society for Experimental Biology andMedicine vol 220 no 4 pp 244ndash248 1999

[48] J Zhou F Guo and Z Qian ldquoEffects of cigarette smoking onantioxidant vitamin and activities of antioxidasesrdquoZhonghuaYuFang Yi Xue Za Zhi vol 31 no 2 pp 67ndash70 1997

[49] M Dietrich G Block E P Norkus et al ldquoSmoking and expo-sure to environmental tobacco smoke decrease some plasmaantioxidants and increase 120574-tocopherol in vivo after adjustmentfor dietary antioxidant intakesrdquo American Journal of ClinicalNutrition vol 77 no 1 pp 160ndash166 2003

[50] J Chavez C Cano A Souki et al ldquoEffect of cigarette smokingon the oxidantantioxidant balance in healthy subjectsrdquo TheAmerican Journal of Therapeutics vol 14 no 2 pp 189ndash1932007

[51] M C Polidori P Mecocci W Stahl and H Sies ldquoCigarettesmoking cessation increases plasma levels of several antioxidantmicronutrients and improves resistance towards oxidative chal-lengerdquo British Journal of Nutrition vol 90 no 1 pp 147ndash1502003

[52] W A Pryor and D F Church ldquoAldehydes hydrogen peroxideand organic radicals asmediators of ozone toxicityrdquo Free RadicalBiology and Medicine vol 11 no 1 pp 41ndash46 1991

[53] J A Last W M Sun and H Witschi ldquoOzone NO andNO2

oxidant air pollutants and morerdquo Environmental HealthPerspectives vol 102 supplement 10 pp 179ndash184 1994

[54] K Kienast M Knorst S Lubjuhn J Muller-Quernheim and RFerlinz ldquoNitrogen dioxide-induced reactive oxygen intermedi-ates production by human alveolarmacrophages and peripheralblood mononuclear cellsrdquo Archives of Environmental Healthvol 49 no 4 pp 246ndash250 1994

[55] D J Guth and R D Mavis ldquoThe effect of lung 120572-tocopherolcontent on the acute toxicity of nitrogen dioxiderdquo Toxicologyand Applied Pharmacology vol 84 no 2 pp 304ndash314 1986

[56] A Sevanian N Elsayed and A D Hacker ldquoEffects of vitamin Edeficiency and nitrogen dioxide exposure on lung lipid peroxi-dation use of lipid epoxides and malonaldehyde as measures ofperoxidationrdquo Journal of Toxicology and Environmental Healthvol 10 no 4-5 pp 743ndash756 1982

[57] F J Kelly and T D Tetley ldquoNitrogen dioxide depletes uric acidand ascorbic acid but not glutathione from lung lining fluidrdquoBiochemical Journal vol 325 part 1 pp 95ndash99 1997

[58] F J Kelly A Blomberg A Frew S THolgate andT SandstromldquoAntioxidant kinetics in lung lavage fluid following exposure ofhumans to nitrogen dioxiderdquo American Journal of Respiratoryand Critical Care Medicine vol 154 no 6 part 1 pp 1700ndash17051996

[59] I M C M Rietjens M C M Poelen R A Hempenius MJ Gijbels and G M Alink ldquoToxicity of ozone and nitrogendioxide to alveolar macrophages comparative study revealingdifferences in their mechanism of toxic actionrdquo Journal ofToxicology and Environmental Health vol 19 no 4 pp 555ndash5681986

[60] V Mohsenin ldquoEffect of vitamin C on NO2

-induced airwayhyperresponsiveness in normal subjects a randomized double-blind experimentrdquoAmerican Review of Respiratory Disease vol136 no 6 pp 1408ndash1411 1987

[61] S M Khopde K I Priyadarsini T Mukherjee P B KulkarniJ G Satav and R K Bhattacharya ldquoDoes 120573-carotene protectmembrane lipids from nitrogen dioxiderdquo Free Radical Biologyand Medicine vol 25 no 1 pp 66ndash71 1998

[62] F Bohm R Edge M Burke and T G Truscott ldquoDietaryuptake of lycopene protects human cells from singlet oxygen

and nitrogen dioxidemdashROS components from cigarette smokerdquoJournal of Photochemistry and Photobiology B Biology vol 64no 2-3 pp 176ndash178 2001

[63] B Gonzalez-Flecha ldquoOxidantmechanisms in response to ambi-ent air particlesrdquoMolecular Aspects ofMedicine vol 25 no (1-2)pp 169ndash182 2004

[64] R A Pinho P C L Silveira L A Silva E Luiz Streck F Dal-Pizzol and J C F Moreira ldquoN-Acetylcysteine and deferoxam-ine reduce pulmonary oxidative stress and inflammation in ratsafter coal dust exposurerdquo Environmental Research vol 99 no 3pp 355ndash360 2005

[65] K Aganasur P Jeff Inmon L A Dailey M C Madden AJ Ghio and J E Gallagher ldquoAir pollution particles mediatedoxidative DNA base damage in a cell free system and in humanairway epithelial cells in relation to particulate metal contentand bioreactivityrdquo Chemical Research in Toxicology vol 14 pp879ndash887 2001

[66] C Hatzis J J Godleski B Gonzalez-Flecha J M Wolfsonand P Koutrakis ldquoAmbient particulate matter exhibits directinhibitory effects on oxidative stress enzymesrdquo EnvironmentalScience and Technology vol 40 no 8 pp 2805ndash2811 2006

[67] F P Possamai S A Junior E B Parisotto et al ldquoAntioxidantintervention compensates oxidative stress in blood of subjectsexposed to emissions from a coal electric-power plant in SouthBrazilrdquo Environmental Toxicology and Pharmacology vol 30no 2 pp 175ndash180 2010

[68] DW Kamp P Graceffa W A Pryor and S AWeitzman ldquoTherole of free radicals in asbestos-induced diseasesrdquo Free RadicalBiology and Medicine vol 12 no 4 pp 293ndash315 1992

[69] C Walker J Everitt and J C Barrett ldquoPossible cellular andmolecular mechanisms for asbestos carcinogenicityrdquoTheAmer-ican Journal of Industrial Medicine vol 21 no 2 pp 253ndash2731992

[70] S Q Luo X Z Liu and C J Wang ldquoInhibitory effect ofgreen tea extract on the carcinogenesis induced by asbestos plusbenzo(a)pyrene in ratrdquo Biomedical and Environmental Sciencesvol 8 no 1 pp 54ndash58 1995

[71] E Lewczuk and H Owczarek ldquoThe role of oxygen free radicalsin asbestos cytotoxicityrdquoMedycyna pracy vol 43 no 4 pp 335ndash342 1992

[72] C L Fattman R J Tan J M Tobolewski and T D OuryldquoIncreased sensitivity to asbestos-induced lung injury in micelacking extracellular superoxide dismutaserdquo Free Radical Biol-ogy and Medicine vol 40 no 4 pp 601ndash607 2006

[73] T K Hei A Xu S X Huang and Y Zhao ldquoMechanism of fibercarcinogenesis from reactive radical species to silencing of the120573igH3 generdquo Inhalation Toxicology vol 18 no 12 pp 985ndash9902006

[74] D Pelclova Z Fenclova P Kacer M Kuzma T Navratil andJ Lebedova ldquoIncreased 8-isoprostane a marker of oxidativestress in exhaled breath condensate in subjects with asbestosexposurerdquo Industrial Health vol 46 no 5 pp 484ndash489 2008

[75] B Marczynski P Rozynek T Kraus S Schlosser H J Raitheland X Baur ldquoLevels of 8-hydroxy-2rsquo-deoxyguanosine in DNAof white blood cells from workers highly exposed to asbestos inGermanyrdquoMutation Research Genetic Toxicology and Environ-mental Mutagenesis vol 468 no 2 pp 195ndash202 2000

[76] V J Thannickal and B L Fanburg ldquoReactive oxygen speciesin cell signalingrdquo American Journal of Physiology Lung CellularandMolecular Physiology vol 279 no 6 pp L1005ndashL1028 2000


[77] B N Ames ldquoDelaying the mitochondrial decay of agingrdquoAnnals of the New York Academy of Sciences vol 1019 pp 406ndash411 2004

[78] R Radi G Peluffo M N Alvarez M Naviliat and A CayotaldquoUnraveling peroxynitrite formation in biological systemsrdquo FreeRadical Biology and Medicine vol 30 no 5 pp 463ndash488 2001

[79] W C Willett ldquoThe Mediterranean diet science and practicerdquoPublic Health Nutrition vol 9 no 1 pp 105ndash110 2006

[80] A Sevanian ADHacker andN Elsayed ldquoInfluence of vitaminE and nitrogen dioxide on lipid peroxidation in rat lung andliver microsomesrdquo Lipids vol 17 no 4 pp 269ndash277 1982

[81] G E Hatch ldquoAsthma inhaled oxidants and dietary antioxi-dantsrdquo American Journal of Clinical Nutrition vol 61 supple-ment 3 pp 625Sndash630S 1995

[82] L Risom P Moslashller and S Loft ldquoOxidative stress-inducedDNA damage by particulate air pollutionrdquo Mutation ResearchFundamental and Molecular Mechanisms of Mutagenesis vol592 no 1-2 pp 119ndash137 2005

[83] L L Greenwell T Moreno and R J Richards ldquoPulmonaryantioxidants exert differential protective effects against urbanand industrial particulate matterrdquo Journal of Biosciences vol 28no 1 pp 101ndash107 2003

[84] A Sperati D D Abeni C Tagesson F Forastiere M MiceliandO Axelson ldquoExposure to indoor background radiation andurinary concentrations of 8-hydroxydeoxyguanosine a markerof oxidative DNA damagerdquo Environmental Health Perspectivesvol 107 no 3 pp 213ndash215 1999

[85] J K Tak and J W Park ldquoThe use of ebselen for radioprotectionin cultured cells and micerdquo Free Radical Biology and Medicinevol 46 no 8 pp 1177ndash1185 2009

[86] S Kilciksiz C Demirel S E Ayhan et al ldquoN-acetylcysteineameliorates nitrosative stress on radiation-inducible damage inrat liverrdquo Journal of BUON vol 16 no 1 pp 154ndash159 2011

[87] S Kilciksiz C Demirel N Erdal et al ldquoThe effect of N-acetylcysteine on biomarkers for radiation-induced oxidativedamage in a rat modelrdquo Acta Medica Okayama vol 62 no 6pp 403ndash409 2008

[88] V Benkovic A H Knezevic D Dikic et al ldquoRadioprotectiveeffects of quercetin and ethanolic extract of propolis in gamma-irradiated micerdquo Archives of Industrial Hygiene and Toxicologyvol 60 no 2 pp 129ndash138 2009

[89] G C Jagetia ldquoRadioprotection and radiosensitization by cur-cuminrdquo Advances in Experimental Medicine and Biology vol595 pp 301ndash320 2007

[90] P Kovacic and R Somanathan ldquoElectromagnetic fields mech-anism cell signaling other bioprocesses toxicity radicalsantioxidants and beneficial effectsrdquo Journal of Receptors andSignal Transduction vol 30 no 4 pp 214ndash226 2010

[91] M Simko and M Mattsson ldquoExtremely low frequency electro-magnetic fields as effectors of cellular responses in vitro pos-sible immune cell activationrdquo Journal of Cellular Biochemistryvol 93 no 1 pp 83ndash92 2004

[92] A V Musaev L F Ismailova A B Shabanova A A Mager-ramov E I Iusifov and A M Gadzhiev ldquoPro- and antioxidanteffect of electromagnetic fields of extremely high frequency(460 MHz) on brain tissues in experimentrdquo Voprosy Kuror-tologii Fizioterapii i Lechebnoi Fizicheskoi Kultury no 2 pp19ndash23 2004

[93] F Ozguner Y Bardak and S Comlekci ldquoProtective effects ofmelatonin and caffeic acid phenethyl ester against retinal oxida-tive stress in long-term use of mobile phone a comparative

studyrdquoMolecular and Cellular Biochemistry vol 282 no 1-2 pp83ndash88 2006

[94] J Jajte M Zmyslony J Palus E Dziubaltowska and ERajkowska ldquoProtective effect of melatonin against in vitro ironions and 7mT 50Hz magnetic field-induced DNA damage inrat lymphocytesrdquoMutation Research vol 483 no (1-2) pp 57ndash64 2001

[95] A Ilhan A Gurel F Armutcu et al ldquoGinkgo biloba preventsmobile phone-induced oxidative stress in rat brainrdquo ClinicaChimica Acta vol 340 no 1-2 pp 153ndash162 2004

[96] M Guney F Ozguner B Oral N Karahan and T Munganldquo900 MHz radiofrequency-induced histopathologic changesand oxidative stress in rat endometrium protection by vitaminsE and CrdquoToxicology and Industrial Health vol 23 no 7 pp 411ndash420 2007

[97] C O Wambi J K Sanzari C M Sayers et al ldquoProtectiveeffects of dietary antioxidants on proton total-body irradiation-mediated hematopoietic cell and animal survivalrdquo RadiationResearch vol 172 no 2 pp 175ndash186 2009

[98] E R Andrade I B M Cruz V V R Andrade et al ldquoEvaluationof the potential protective effects of ad libitum black grapejuice against liver oxidative damage in whole-body acute X-irradiated ratsrdquo Food and Chemical Toxicology vol 49 no 4 pp1026ndash1032 2011

[99] G G Nair and C K K Nair ldquoProtection of cellular DNA andmembrane from 120574-radiation-induced damages and enhance-ment in DNA repair by sesamolrdquo Cancer Biotherapy andRadiopharmaceuticals vol 25 no 6 pp 629ndash635 2010

[100] MA El-Missiry T A FayedM R El-Sawy andAA El-SayedldquoAmeliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injuryrdquo Ecotoxicology andEnvironmental Safety vol 66 no 2 pp 278ndash286 2007

[101] M Karbownik and R J Reiter ldquoAntioxidative effects of mela-tonin in protection against cellular damage caused by ionizingradiationrdquo Experimental Biology and Medicine vol 225 no 1pp 9ndash22 2000

[102] C K K Nair P U Devi R Shimanskaya et al ldquoWatersoluble vitamin E (TMG) as a radioprotectorrdquo Indian Journalof Experimental Biology vol 41 no 12 pp 1365ndash1371 2003

[103] E Noaman A M Zahran A M Kamal and M F OmranldquoVitamin E and selenium administration as a modulator ofantioxidant defense system biochemical assessment and mod-ificationrdquo Biological Trace Element Research vol 86 no 1 pp55ndash64 2002

[104] M Berbee Q Fu M Boerma J Wang K S Kumar and MHauer-Jensen ldquo120574-Tocotrienol ameliorates intestinal radiationinjury and reduces vascular oxidative stress after total-bodyirradiation by an HMG-CoA Reductase-dependent mecha-nismrdquo Radiation Research vol 171 no 5 pp 596ndash605 2009

[105] M Srinivasan N Devipriya K B Kalpana and V P MenonldquoLycopene an antioxidant and radioprotector against 120574-radiation-induced cellular damages in cultured human lympho-cytesrdquo Toxicology vol 262 no 1 pp 43ndash49 2009

[106] Y Hu D Guo P Liu et al ldquoBioactive components from thetea polyphenols influence on endogenous antioxidant defensesystem and modulate inflammatory cytokines after total-bodyirradiation in micerdquo Phytomedicine vol 18 no 11 pp 970ndash9752011

[107] F I Wolf S Fasanella B Tedesco et al ldquoPeripheral lymphocyte8-OHdG levels correlate with age-associated increase of tissueoxidative DNA damage in Sprague-Dawley rats Protective


effects of caloric restrictionrdquo Experimental Gerontology vol 40no 3 pp 181ndash188 2005

[108] G Guler Z Turkozer A Tomruk and N Seyhan ldquoThe protec-tive effects of N-acetyl-L-cysteine and Epigallocatechin-3- gal-late on electric field-induced hepatic oxidative stressrdquo Interna-tional Journal of Radiation Biology vol 84 no 8 pp 669ndash6802008

[109] E Ozgur G Guler and N Seyhan ldquoMobile phone radiation-induced free radical damage in the liver is inhibited by theantioxidants N-acetyl cysteine and epigallocatechin-gallaterdquoInternational Journal of Radiation Biology vol 86 no 11 pp935ndash945 2010

[110] M Simko ldquoCell type specific redox status is responsible fordiverse electromagnetic field effectsrdquo Current Medicinal Chem-istry vol 14 no 10 pp 1141ndash1152 2007

[111] R J Reiter ldquoMelatonin suppression by static and extremely lowfrequency electromagnetic fields relationship to the reportedincreased incidence of cancerrdquo Reviews on EnvironmentalHealth vol 10 no 3-4 pp 171ndash186 1994

[112] M Naziroglu and N Gumral ldquoModulator effects of L-carnitineand selenium on wireless devices (245 GHz)-induced oxidativestress and electroencephalography records in brain of ratrdquoInternational Journal of Radiation Biology vol 85 no 8 pp680ndash689 2009

[113] J G Peak M J Peak R A Sikorski and R A Jones ldquoInductionof DNA-protein cross-links in human cells by ultraviolet andvisible radiations action spectrumrdquo Photochemistry and Photo-biology vol 41 no 3 pp 295ndash302 1988

[114] B C Beehler J Przybyszewski H B Box and M F Kulesz-Martin ldquoFormation of 8-hydroxydeoxyguanosine within DNAof mouse keratinocytes exposed in culture to UVB and H

2

O2

rdquoCarcinogenesis vol 13 no 11 pp 2003ndash2007 1992

[115] T R Berton D L Mitchell S M Fischer and M F LocniskarldquoEpidermal proliferation but not the quantity of DNA photo-damage is correlated with UV-induced mouse skin carcinogen-esisrdquo Journal of Investigative Dermatology vol 109 no 3 pp340ndash347 1997

[116] G Li D L Mitchell V C Ho J C Reed and V A TronldquoDecreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic micerdquo American Journal ofPathology vol 148 no 4 pp 1113ndash1123 1996

[117] H Masaki ldquoRole of antioxidants in the skin anti-aging effectsrdquoJournal of Dermatological Science vol 58 no 2 pp 85ndash90 2010

[118] F McArdle L E Rhodes R Parslew C I A Jack P SFriedmann andM J Jackson ldquoUVR-induced oxidative stress inhuman skin in vivo effects of oral vitamin C supplementationrdquoFree Radical Biology andMedicine vol 33 no 10 pp 1355ndash13622002

[119] P G Humbert M Haftek P Creidi et al ldquoTopical ascorbic acidon photoaged skin Clinical topographical and ultrastructuralevaluation double-blind study vs placebordquo Experimental Der-matology vol 12 no 3 pp 237ndash244 2003

[120] E F Ritter M Axelrod K W Minn et al ldquoModulation ofultraviolet light-induced epidermal damage beneficial effects oftocopherolrdquo Plastic and Reconstructive Surgery vol 100 no 4pp 973ndash980 1997

[121] L Packer S U Weber and G Rimbach ldquoMolecular aspects of120572-tocotrienol antioxidant action and cell signallingrdquo Journal ofNutrition vol 131 no 2 pp 369Sndash373S 2001

[122] W Stahl U Heinrich H Jungmann H Sies and H TronnierldquoCarotenoids and carotenoids plus vitamin E protect against

ultraviolet light-induced erythema in humansrdquo American Jour-nal of Clinical Nutrition vol 71 no 3 pp 795ndash798 2000

[123] L H Kligman and A M Kligman ldquoThe nature of photoagingits prevention and repairrdquo Photodermatology vol 3 no 4 pp215ndash227 1986

[124] W Stahl H Mukhtar F Afaq and H Sies ldquoVitamins andpolyphenols XE polyphenols in systemic photoprotectionrdquo inSkin Aging B Gilchrest and J Krutmann Eds Springer BerlinGermany 2006

[125] H Sies and W Stahl ldquoCarotenoids and UV protectionrdquo Photo-chemical and Photobiological Sciences vol 3 no 8 pp 749ndash7522004

[126] S Cho D H Lee C H Won et al ldquoDifferential effects of low-dose and high-dose beta-carotene supplementation on the signsof photoaging and type I procollagen gene expression in humanskin in vivordquo Dermatology vol 221 no 2 pp 160ndash171 2010

[127] Y Shindo E Witt and L Packer ldquoAntioxidant defense mecha-nisms in murine epidermis and dermis and their responses toultraviolet lightrdquo Journal of Investigative Dermatology vol 100no 3 pp 260ndash265 1993

[128] L Packer and G Valacchi ldquoAntioxidants and the response ofskin to oxidative stress vitamin E as a key indicatorrdquo SkinPharmacology and Applied Skin Physiology vol 15 no 5 pp282ndash290 2002

[129] J J Thiele ldquoOxidative targets in the stratum corneum anew basis for antioxidative strategiesrdquo Skin Pharmacology andApplied Skin Physiology vol 14 no 1 pp 87ndash91 2001

[130] J D Ribaya-Mercado M Garmyn B A Gilchrest and RM Russell ldquoSkin lycopene is destroyed preferentially over 120573-carotene during ultraviolet irradiation in humansrdquo Journal ofNutrition vol 125 no 7 pp 1854ndash1859 1995

[131] U Heinrich C Gartner M Wiebusch et al ldquoSupplementationwith 120573-carotene or a similar amount of mixed carotenoids pro-tects humans fromUV-induced erythemardquo Journal of Nutritionvol 133 no 1 pp 98ndash101 2003

[132] J Lee S Jiang N Levine and R R Watson ldquoCarotenoidsupplementation reduces erythema in human skin after sim-ulated solar radiation exposurerdquo Proceedings of the Society forExperimental Biology and Medicine vol 223 no 2 pp 170ndash1742000

[133] W Stahl A Junghans B deBoer E SDriominaK Briviba andH Sies ldquoCarotenoid mixtures protect multilamellar liposomesagainst oxidative damage synergistic effects of lycopene andluteinrdquo FEBS Letters vol 427 no 2 pp 305ndash308 1998

[134] O Aust W Stahl H Sies H Tronnier and U Heinrich ldquoSup-plementation with tomato-based products increases lycopenephytofluene and phytoene levels in human serum and protectsagainst UV-light-induced erythemardquo International Journal forVitamin and Nutrition Research vol 75 no 1 pp 54ndash60 2005

[135] S L Yeh C S Huang andM L Hu ldquoLycopene enhances UVA-induced DNA damage and expression of heme oxygenase-1in cultured mouse embryo fibroblastsrdquo European Journal ofNutrition vol 44 no 6 pp 365ndash370 2005

[136] F Afaq and H Mukhtar ldquoPhotochemoprevention by botanicalantioxidantsrdquo Skin Pharmacology and Physiology vol 15 pp297ndash306 2002

[137] S K Katiyar N Ahmad and H Mukhtar ldquoGreen tea and skinrdquoArchives of Dermatology vol 136 no 8 pp 989ndash994 2000

[138] S K Katiyar ldquoSkin photoprotection by green tea antioxi-dant and immunomodulatory effectsrdquo Current Drug TargetsImmune Endocrine and Metabolic Disorders vol 3 no 3 pp234ndash242 2003


[139] S K Katiyar M Vaid H van Steeg and S M Meeran ldquoGreentea polyphenols prevent uv-induced immunosuppression byrapid repair of DNA damage and enhancement of nucleotideexcision repair genesrdquo Cancer Prevention Research vol 3 no 2pp 179ndash189 2010

[140] Y P Lu Y R Lou Q Y Peng J G Xie P Nghiem and A HConney ldquoEffect of caffeine on the ATRChk1 pathway in theepidermis of UVB-irradiated micerdquo Cancer Research vol 68no 7 pp 2523ndash2529 2008

[141] R P Singh and R Agarwal ldquoFlavonoid antioxidant silymarinand skin cancerrdquo Antioxidants and Redox Signaling vol 4 no4 pp 655ndash663 2002

[142] F BoninaM Lanza LMontenegro et al ldquoFlavonoids as poten-tial protective agents against photo-oxidative skin damagerdquoInternational Journal of Pharmaceutics vol 145 no 1-2 pp 87ndash94 1996

[143] H Wei R Bowen Q Cai S Barnes and Y Wang ldquoAntioxidantand antipromotional effects of the soybean isoflavone genis-teinrdquo Proceedings of the Society for Experimental Biology andMedicine vol 208 no 1 pp 124ndash130 1995

[144] C Saliou G Rimbach H Moini et al ldquoSolar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated bya French maritime pine bark extractrdquo Free Radical Biology andMedicine vol 30 no 2 pp 154ndash160 2001

[145] D Bagchi M Bagchi E A Hassoun and S J Stohs ldquoIn vitroand in vivo generation of reactive oxygen species DNA dam-age and lactate dehydrogenase leakage by selected pesticidesrdquoToxicology vol 104 no 1ndash3 pp 129ndash140 1995

[146] V L de Liz Oliveira Cavalli D Cattani C E Heinz Rieg et alldquoRoundup disrupts male reproductive functions by triggeringcalcium-mediated cell death in rat testis and Sertoli cellsrdquo FreeRadical Biology and Medicine vol 65 pp 335ndash346 2013

[147] S Olgun andH P Misra ldquoPesticides induced oxidative stress inthymocytesrdquoMolecular and Cellular Biochemistry vol 290 no1-2 pp 137ndash144 2006

[148] E Hassoun M Bagchi D Bagchi and S J Stohs ldquoComparativestudies on lipid peroxidation and DNA-single strand breaksinduced by lindane DDT chlordane and endrin in ratsrdquoComparative Biochemistry and Physiology C vol 104 no 3 pp427ndash431 1993

[149] J S Bus S D Aust and J E Gibson ldquoParaquat toxicityproposed mechanism of action involving lipid peroxidationrdquoEnvironmental Health Perspectives vol 16 pp 139ndash146 1976

[150] I N Perez-Maldonado C Herrera L E Batres R Gonzalez-Amaro F Dıaz-Barriga and L Yanez ldquoDDT-induced oxidativedamage in human blood mononuclear cellsrdquo EnvironmentalResearch vol 98 no 2 pp 177ndash184 2005

[151] A P Senft T P Dalton D W Nebert M B Genter R JHutchinson and H G Shertzer ldquoDioxin increases reactiveoxygen production in mouse liver mitochondriardquo Toxicologyand Applied Pharmacology vol 178 no 1 pp 15ndash21 2002

[152] O Ciftci S Tanyildizi and A Godekmerdan ldquoProtective effectof curcumin on immune system and body weight gain on ratsintoxicatedwith 2378-Tetrachlorodibenzo-p-dioxin (TCDD)rdquoImmunopharmacology and Immunotoxicology vol 32 no 1 pp99ndash104 2010

[153] Y Hung G S Huang V M Sava V A Blagodarsky and MHong ldquoProtective effects of tea melanin against 2378-tetra-chlorodibenzo-p-dioxin-induced toxicity antioxidant activityand aryl hydrocarbon receptor suppressive effectrdquo Biologicaland Pharmaceutical Bulletin vol 29 no 11 pp 2284ndash2291 2006

[154] F Gultekin N Delibas S Yasar and I Kilinc ldquoIn vivo changesin antioxidant systems and protective role of melatonin and acombination of vitamin C and vitamin E on oxidative damagein erythrocytes induced by chlorpyrifos-ethyl in ratsrdquo Archivesof Toxicology vol 75 no 2 pp 88ndash96 2001

[155] Y Zhu A L Kalen L Li et al ldquoPolychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated byantioxidants after exposurerdquo Free Radical Biology andMedicinevol 47 no 12 pp 1762ndash1771 2009

[156] P Ramadass P Meerarani M Toborek LW Robertson and BHennig ldquoDietary flavonoids modulate PCB-induced oxidativestress CYP1A1 induction and AhR-DNA binding activity invascular endothelial cellsrdquo Toxicological Sciences vol 76 no 1pp 212ndash219 2003

[157] S Park J Jang C Chen H Na and Y Surh ldquoA formulatedred ginseng extract rescues PC12 cells from PCB-inducedoxidative cell death through Nrf2-mediated upregulation ofheme oxygenase-1 and glutamate cysteine ligaserdquo Toxicologyvol 278 no 1 pp 131ndash139 2010

[158] N Sridevi P Venkataraman K Senthilkumar G Krishnamoor-thy and J Arunakaran ldquoOxidative stress modulates membranebound ATPases in brain regions of PCB (Aroclor 1254) exposedrats protective role of 120572-tocopherolrdquo Biomedicine and Pharma-cotherapy vol 61 no 7 pp 435ndash440 2007

[159] P Murugesan T Muthusamy K Balasubramanian and JArunakaran ldquoStudies on the protective role of vitamin C andE against polychlorinated biphenyl (Aroclor 1254)mdashinducedoxidative damage in Leydig cellsrdquo Free Radical Research vol 39no 11 pp 1259ndash1272 2005

[160] O Ciftci I Ozdemir S Tanyildizi S Yildiz and H OguzturkldquoAntioxidative effects of curcumin 120573-myrcene and 18-cineoleagainst 2378-tetrachlorodibenzo-p-dioxin-induced oxidativestress in rats liverrdquo Toxicology and Industrial Health vol 27 no5 pp 447ndash453 2011

[161] F Karatas S Servi H Kara T R Kiran and S Saydam ldquoInvesti-gation of oxidative status of the 2-furan-2-yl-1H-benzimidazolein ratsrdquo Biological Trace Element Research vol 126 no 1ndash3 pp214ndash221 2008

[162] T Ishida T Takeda T Koga et al ldquoAttenuation of 2378-tetrachlorodibenzo-p-dioxin toxicity by resveratrol a compar-ative study with different routes of administrationrdquo Biologicaland Pharmaceutical Bulletin vol 32 no 5 pp 876ndash881 2009

[163] H Turkez F Geyikoglu M I Yousef B Togar and SVancelik ldquoPropolis alleviates 2378-Tetrachlorodibenzo-p-dioxin-induced histological changes oxidative stress and DNAdamage in rat liverrdquo Toxicology and Industrial Health vol 29no 8 pp 677ndash685 2012

[164] N H Song X L Yin G F Chen and H Yang ldquoBiologicalresponses of wheat (Triticum aestivum) plants to the herbicidechlorotoluron in soilsrdquo Chemosphere vol 68 no 9 pp 1779ndash1787 2007

[165] D Bagchi G Bhattacharya and S J Stohs ldquoIn vitro and in vivoinduction of heat shock (stress) protein (Hsp) gene expressionby selected pesticidesrdquoToxicology vol 112 no 1 pp 57ndash68 1996

[166] G E Kisby J F Muniz J Scherer et al ldquoOxidative stress andDNA damage in agricultural workersrdquo Journal of Agromedicinevol 14 no 2 pp 206ndash214 2009

[167] X Yi H Ding Y Lu H Liu M Zhang and W Jiang ldquoEffectsof long-term alachlor exposure on hepatic antioxidant defenseand detoxifying enzyme activities in crucian carp (Carassiusauratus)rdquo Chemosphere vol 68 no 8 pp 1576ndash1581 2007


[168] C Kesavachandran V K Singh N Mathur et al ldquoPossiblemechanism of pesticide toxicity-related oxidative stress leadingto airway narrowingrdquo Redox Report vol 11 no 4 pp 159ndash1622006

[169] G F Combs Jr and F J Peterson ldquoProtection against acuteparaquat toxicity by dietary selenium in the chickrdquo Journal ofNutrition vol 113 no 3 pp 538ndash545 1983

[170] M Glass M W Sutherland H J Forman and A B FisherldquoSelenium deficiency potentiates paraquat-induced lipid per-oxidation in isolated perfused rat lungrdquo Journal of AppliedPhysiology vol 59 no 2 pp 619ndash622 1985

[171] W H Cheng Y S Ho B A Valentine D A Ross G FCombs Jr and X G Lei ldquoCellular glutathione peroxidase is themediator of body selenium to protect against paraquat lethalityin transgenicmicerdquo Journal of Nutrition vol 128 no 7 pp 1070ndash1076 1998

[172] M Takizawa K Komori Y Tampo and M Yonaha ldquoParaquat-induced oxidative stress and dysfunction of cellular redoxsystems including antioxidative defense enzymes glutathioneperoxidase and thioredoxin reductaserdquo Toxicology in Vitro vol21 no 3 pp 355ndash363 2007

[173] M Aono H Saji K Fujiyama M Sugita N Kondo and KTanaka ldquoDecrease in activity of glutathione reductase enhancesparaquat sensitivity in transgenic Nicotiana tabacumrdquo PlantPhysiology vol 107 no 2 pp 645ndash648 1995

[174] O Akturk H Demirin R Sutcu N Yilmaz H Koylu andI Altuntas ldquoThe effects of diazinon on lipid peroxidationand antioxidant enzymes in rat heart and ameliorating role ofvitamin E and vitamin Crdquo Cell Biology and Toxicology vol 22no 6 pp 455ndash461 2006

[175] R S Verma A Mehta and N Srivastava ldquoIn vivo chlorpyrifosinduced oxidative stress attenuation by antioxidant vitaminsrdquoPesticide Biochemistry and Physiology vol 88 no 2 pp 191ndash1962007

[176] I Altuntas N Delibas and R Sutcu ldquoThe effects of organo-phosphate insecticide methidathion on lipid peroxidation andanti-oxidant enzymes in rat erythrocytes role of vitamins E andCrdquoHuman and Experimental Toxicology vol 21 no 12 pp 681ndash685 2002

[177] A Goel V Dani and D K Dhawan ldquoProtective effects ofzinc on lipid peroxidation antioxidant enzymes and hepatichistoarchitecture in chlorpyrifos-induced toxicityrdquo Chemico-Biological Interactions vol 156 no 2-3 pp 131ndash140 2005

[178] D E Stevenson E F Walborg Jr D W North et al ldquoMono-graph reassessment of human cancer risk of aldrindieldrinrdquoToxicology Letters vol 109 no 3 pp 123ndash186 1999

[179] S Bachowski Y Xu D E Stevenson E F Walborg Jr and JE Klaunig ldquoRole of oxidative stress in the selective toxicity ofdieldrin in the mouse liverrdquo Toxicology and Applied Pharmacol-ogy vol 150 no 2 pp 301ndash309 1998

[180] D E Stevenson J P Kehrer K L Kolaja E FWalborg Jr and JE Klaunig ldquoEffect of dietary antioxidants on dieldrin-inducedhepatotoxicity in micerdquo Toxicology Letters vol 75 no 1ndash3 pp177ndash183 1995

[181] J E Klaunig Y Xu S Bachowski et al ldquoOxidative stress innongenotoxic carcinogenesisrdquo Toxicology Letters vol 82-83 pp683ndash691 1995

[182] S J Stohs ldquoOxidative stress induced by 2378-tetrachloro-dibenzo-p-dioxin (TCDD)rdquo Free Radical Biology and Medicinevol 9 no 1 pp 79ndash90 1990

[183] N Z Alsharif and E A Hassoun ldquoProtective effects of vitaminA and vitamin E succinate against 2378-tetrachlorodibenzo-p-dioxin (TCDD)-induced body wasting hepatomegaly thymicatrophy production of reactive oxygen species and DNA dam-age in C57BL6J micerdquo Basic and Clinical Pharmacology andToxicology vol 95 no 3 pp 131ndash138 2004

[184] S Wen F Yang Y Gong et al ldquoElevated levels of urinary 8-hydroxy-21015840-deoxyguanosine in male electrical and electronicequipment dismantlingworkers exposed to high concentrationsof polychlorinated dibenzo-p-dioxins and dibenzofurans poly-brominated diphenyl ethers and polychlorinated biphenylsrdquoEnvironmental Science and Technology vol 42 no 11 pp 4202ndash4207 2008

[185] Y Song B A Wagner H J Lehmler and G R BuettnerldquoSemiquinone radicals from oxygenated polychlorinatedbiphenyls electron paramagnetic resonance studiesrdquo ChemicalResearch in Toxicology vol 21 no 7 pp 1359ndash1367 2008

[186] K Shimizu F Ogawa J JThiele S Bae and S Sato ldquoLipid per-oxidation is enhanced in Yusho victims 35 years after accidentalpoisoning with polychlorinated biphenyls in Nagasaki JapanrdquoJournal of Applied Toxicology vol 27 no 2 pp 195ndash197 2007

[187] K Shimizu F Ogawa and S Sato ldquoEstimation of total antiox-idant power in the serum of Yusho victimsrdquo Fukuoka IgakuZasshi vol 98 no 5 pp 141ndash142 2007

[188] S Banudevi G Krishnamoorthy P Venkataraman C VigneshM M Aruldhas and J Arunakaran ldquoRole of 120572-tocopherol onantioxidant status in liver lung and kidney of PCB exposedmalealbino ratsrdquo Food and Chemical Toxicology vol 44 no 12 pp2040ndash2046 2006

[189] G Krishnamoorthy P Venkataraman A Arunkumar R CVignesh M M Aruldhas and J Arunakaran ldquoAmeliorativeeffect of vitamins (120572-tocopherol and ascorbic acid) on PCB(Aroclor 1254) induced oxidative stress in rat epididymalspermrdquo Reproductive Toxicology vol 23 no 2 pp 239ndash2452007

[190] C Zhou and C Zhang ldquoProtective effects of antioxidantvitamins on Aroclor 1254-induced toxicity in cultured chickenembryo hepatocytesrdquo Toxicology in Vitro vol 19 no 5 pp 665ndash673 2005

[191] P Venkataraman G Krishnamoorthy G Vengatesh N Srini-vasan M M Aruldhas and J Arunakaran ldquoProtective roleof melatonin on PCB (Aroclor 1254) induced oxidative stressand changes in acetylcholine esterase and membrane boundATPases in cerebellum cerebral cortex and hippocampus ofadult rat brainrdquo International Journal of Developmental Neuro-science vol 26 no 6 pp 585ndash591 2008

[192] P Elumalai G Krishnamoorthy K Selvakumar R ArunkumarP Venkataraman and J Arunakaran ldquoStudies on the protectiverole of lycopene against polychlorinated biphenyls (Aroclor1254)-induced changes in StAR protein and cytochrome P450scc enzyme expression on Leydig cells of adult ratsrdquo Reproduc-tive Toxicology vol 27 no 1 pp 41ndash45 2009

[193] J R Chang and D Q Xu ldquoEffects of formaldehyde on theactivity of superoxide dismutases and glutathione peroxidaseand the concentration of malondialdehyderdquoWei Sheng Yan Jiuvol 35 no 5 pp 653ndash655 2006

[194] E Kose M Sarsılmaz U Tas et al ldquoRose oil inhalationprotects against formaldehyde-induced testicular damage inratsrdquo Andrologia vol 44 supplement 1 pp 342ndash348 2011

[195] I Zararsiz S Meydan M Sarsilmaz A Songur O A Ozenand S Sogut ldquoProtective effects of omega-3 essential fatty acids


against formaldehyde-induced cerebellar damage in ratsrdquo Toxi-cology and Industrial Health vol 27 no 6 pp 489ndash495 2011

[196] I ZararsizM Sarsilmaz U Tas I Kus SMeydan and E OzanldquoProtective effect of melatonin against formaldehyde-inducedkidney damage in ratsrdquo Toxicology and Industrial Health vol23 no 10 pp 573ndash579 2007

[197] J A Brent and B H Rumack ldquoRole of free radicals in toxichepatic injury II Are free radicals the cause of toxin-inducedliver injuryrdquo Journal of Toxicology Clinical Toxicology vol 31no 1 pp 173ndash196 1993

[198] C Tsai Y Hsu W Chen et al ldquoHepatoprotective effect of elec-trolyzed reduced water against carbon tetrachloride-inducedliver damage in micerdquo Food and Chemical Toxicology vol 47no 8 pp 2031ndash2036 2009

[199] J D Morrow J A Awad T Kato et al ldquoFormation of novelnon-cyclooxygenase-derived prostanoids (F2-lsoprostanes) incarbon tetrachloride hepatotoxicity an animal model of lipidperoxidationrdquo Journal of Clinical Investigation vol 90 no 6 pp2502ndash2507 1992

[200] S Basu ldquoCarbon tetrachloride-induced lipid peroxidationeicosanoid formation and their regulation by antioxidant nutri-entsrdquo Toxicology vol 189 no 1-2 pp 113ndash127 2003

[201] F Ozturk M Gul B Ates et al ldquoProtective effect of apricot(Prunus armeniaca L) on hepatic steatosis and damage inducedby carbon tetrachloride in Wistar ratsrdquo British Journal ofNutrition vol 102 no 12 pp 1767ndash1775 2009

[202] O A Adaramoye ldquoComparative effects of vitamin E and kolavi-ron (a biflavonoid fromGarcinia kola) on carbon tetrachloride-induced renal oxidative damage in micerdquo Pakistan Journal ofBiological Sciences vol 12 no 16 pp 1146ndash1151 2009

[203] Y W Hsu C F Tsai W C Chuang W K Chen Y CHo and F J Lu ldquoProtective effects of silica hydride againstcarbon tetrachloride-induced hepatotoxicity inmicerdquo Food andChemical Toxicology vol 48 no 6 pp 1644ndash1653 2010

[204] E R Sindhu A P Firdous K C Preethi and R KuttanldquoCarotenoid lutein protects rats from paracetamol- carbontetrachloride- and ethanol-induced hepatic damagerdquo Journal ofPharmacy and Pharmacology vol 62 no 8 pp 1054ndash1060 2010

[205] H Lee L Li H Kim et al ldquoThe protective effects of Curcumalonga Linn extract on carbon tetrachloride-induced hepatotox-icity in rats via upregulation of Nrf2rdquo Journal of Microbiologyand Biotechnology vol 20 no 9 pp 1331ndash1338 2010

[206] T Annadurai S Vigneshwari R Thirukumaran P AThomas and P Geraldine ldquoAcetyl-L-carnitine prevents carbontetrachloride-induced oxidative stress in various tissues ofWistar ratsrdquo Journal of Physiology and Biochemistry vol 67 no4 pp 519ndash530 2011

[207] B O Cho H W Ryu C H Jin et al ldquoBlackberry extractattenuates oxidative stress through up-regulation of Nrf2-dependent antioxidant enzymes in carbon tetrachloride-treatedratsrdquo Journal of Agricultural and Food Chemistry vol 59 no 21pp 11442ndash11448 2011

[208] M H Hassan M Edfaway A Mansour and A A HamedldquoAntioxidant and antiapoptotic effects of capsaicin againstcarbon tetrachloride-induced hepatotoxicity in ratsrdquoToxicologyand Industrial Health vol 28 no 5 pp 428ndash438 2012

[209] M Bhadauria ldquoPropolis prevents hepatorenal injury inducedby chronic exposure to carbon tetrachloriderdquo Evidence-BasedComplementary and Alternative Medicine vol 2012 Article ID235358 12 pages 2012

[210] M Aranda C D Albendea F Lostale et al ldquoIn vivo hepaticoxidative stress because of carbon tetrachloride toxicity pro-tection by melatonin and pinolinerdquo Journal of Pineal Researchvol 49 no 1 pp 78ndash85 2010

[211] K S Almurshed ldquoProtective effect of black and green tea againstcarbon tetrachloride-induced oxidative stress in ratsrdquo SaudiMedical Journal vol 27 no 12 pp 1804ndash1809 2006

[212] E A Hassoun and S Ray ldquoThe induction of oxidative stressand cellular death by the drinking water disinfection by-products dichloroacetate and trichloroacetate in J774A1 cellsrdquoComparative Biochemistry and Physiology C Toxicology andPharmacology vol 135 no 2 pp 119ndash128 2003

[213] A K Yadav A Bracher S F Doran et al ldquoMechanismsand modification of chlorine-induced lung injury in animalsrdquoProceedings of the American Thoracic Society vol 7 no 4 pp278ndash283 2010

[214] M Leustik S Doran A Bracher et al ldquoMitigation of chlorine-induced lung injury by low-molecular-weight antioxidantsrdquoAmerican Journal of Physiology Lung Cellular and MolecularPhysiology vol 295 no 5 pp L733ndashL743 2008

[215] S G Zarogiannis A Jurkuvenaite S Fernandez et al ldquoAscor-bate and deferoxamine administration after chlorine exposuredecrease mortality and lung injury in micerdquo American Journalof Respiratory Cell andMolecular Biology vol 45 no 2 pp 386ndash392 2011

[216] Y Kawai Y Matsui H Kondo et al ldquoGalloylated catechins aspotent inhibitors of hypochlorous acid-induced DNA damagerdquoChemical Research in Toxicology vol 21 no 7 pp 1407ndash14142008

[217] D Tan L C Manchester R J Reiter W Qi M Karbownikand J R Calvo ldquoSignificance of melatonin in antioxidativedefense system Reactions and productsrdquo Biological Signals andReceptors vol 9 no 3-4 pp 137ndash159 2000

[218] O N Medina-Campos D Barrera S Segoviano-Murillo etal ldquoS-allylcysteine scavenges singlet oxygen and hypochlorousacid and protects LLC-PK1 cells of potassium dichromate-induced toxicityrdquo Food and Chemical Toxicology vol 45 no 10pp 2030ndash2039 2007

[219] R Arguello-Garcıa O N Medina-Campos N Perez-Hernandez J Pedraza-Chaverrı and G Ortega-PierresldquoHypochlorous acid scavenging activities of thioallylcompounds from garlicrdquo Journal of Agricultural and FoodChemistry vol 58 no 21 pp 11226ndash11233 2010

[220] M Strosova J Karlovska C M Spickett T Grune ZOrszagova and L Horakova ldquoOxidative injury induced byhypochlorous acid to Ca-ATPase from sarcoplasmic reticulumof skeletal muscle and protective effect of troloxrdquo GeneralPhysiology and Biophysics vol 28 no 2 pp 195ndash209 2009

[221] A C Carr T Tijerina and B Frei ldquoVitamin C protects againstand reverses specific hypochlorons acid- and chloramine-dependent modifications of low-density lipoproteinrdquo Biochem-ical Journal vol 346 part 2 pp 491ndash499 2000

[222] B M Rezk G R M M Haenen W J F van der Vijgh andA Bast ldquoLipoic Acid Protects Efficiently only against a SpecificForm of Peroxynitrite-induced Damagerdquo Journal of BiologicalChemistry vol 279 no 11 pp 9693ndash9697 2004

[223] S Schaffer G P Eckert W E Muller et al ldquoHypochlorousacid scavenging properties of local Mediterranean plant foodsrdquoLipids vol 39 no 12 pp 1239ndash1247 2004

[224] H Y Peng Y C Chu S J Chen and S T Chou ldquoHepatoprotec-tion of chlorella against carbon tetrachloride-induced oxidativedamage in ratsrdquo In Vivo vol 23 no 5 pp 747ndash754 2009


[225] K Jomova andM Valko ldquoAdvances in metal-induced oxidativestress and human diseaserdquo Toxicology vol 283 no 2-3 pp 65ndash87 2011

[226] M Oliva J J Vicente C Gravato L Guilhermino and M LGalindo-Riano ldquoOxidative stress biomarkers in Senegal soleSolea senegalensis to assess the impact of heavymetal pollutionin a Huelva estuary (SW Spain) seasonal and spatial variationrdquoEcotoxicology and Environmental Safety vol 75 no 1 pp 151ndash162 2012

[227] U J Yang T S Park and S M Shim ldquoProtective effect ofchlorophyllin and lycopene fromwater spinach extract on cyto-toxicity and oxidative stress induced by heavy metals in humanhepatoma cellsrdquo Journal of Toxicology and EnvironmentalHealthA vol 76 no 23 pp 1307ndash1315 2013

[228] H Xing S Li Z Wang X Gao S Xu and X WangldquoOxidative stress response and histopathological changes due toatrazine and chlorpyrifos exposure in common carprdquo PesticideBiochemistry and Physiology vol 103 no 1 pp 74ndash80 2012

[229] S Eroglu D Pandir F G Uzun and H Bas ldquoProtective roleof vitamins C and E in diclorvos-induced oxidative stress inhuman erythrocytes in vitrordquo Biological Research vol 46 no1 pp 33ndash38 2013

[230] R Demirel H Mollaoglu Y Yesilyurt et al ldquoNoise inducesoxidative stress in ratrdquo European Journal of General Medicinevol 6 no 1 pp 20ndash24 2009

[231] D Henderson E C Bielefeld K C Harris and B H Hu ldquoTherole of oxidative stress in noise-induced hearing lossrdquo Ear andHearing vol 27 no 1 pp 1ndash19 2006

[232] S Manikandan and R S Devi ldquoAntioxidant property of120572-asarone against noise-stress-induced changes in differentregions of rat brainrdquo Pharmacological Research vol 52 no 6pp 467ndash474 2005

[233] S Manikandan R Srikumar N J Parthasarathy and R SDevi ldquoProtective effect of Acorus calamus Linn on free radicalscavengers and lipid peroxidation in discrete regions of brainagainst noise stress exposed ratrdquo Biological amp PharmaceuticalBulletin vol 28 no 12 pp 2327ndash2330 2005

[234] F Ozguner A Altinbas M Ozaydin et al ldquoMobile phone-induced myocardial oxidative stress protection by a novelantioxidant agent caffeic acid phenethyl esterrdquo Toxicology andIndustrial Health vol 21 no 9 pp 223ndash230 2005

[235] L E van Campen W J Murphy J R Franks P I MathiasandM A Toraason ldquoOxidative DNAdamage is associated withintense noise exposure in the ratrdquoHearing Research vol 164 no1-2 pp 29ndash38 2002

[236] G Lorito P Giordano S Prosser A Martini and S Hatzopou-los ldquoNoise-induced hearing loss a study on the pharmaco-logical protection in the Sprague Dawley rat with N-acetyl-cysteinerdquo Acta Otorhinolaryngologica Italica vol 26 no 3 pp133ndash139 2006

[237] D L Ewert J Lu W Li X Du R Floyd and R KopkeldquoAntioxidant treatment reduces blast-induced cochlear damageand hearing lossrdquoHearing Research vol 285 no 1-2 pp 29ndash392012

[238] OW Guthrie ldquoDynamic compartmentalization of DNA repairproteins within spiral ganglion neurons in response to noisestressrdquo International Journal of Neuroscience vol 122 no 12 pp757ndash766 2012

[239] L D Fechter ldquoOxidative stress a potential basis for potentiationof noise-induced hearing lossrdquo Environmental Toxicology andPharmacology vol 19 no 3 pp 543ndash546 2005

[240] J D Hackney W S Linn R D Buckley et al ldquoVitamin Esupplementation and respiratory effects of ozone in humansrdquoJournal of Toxicology and Environmental Health vol 7 no 3-4pp 383ndash390 1981

[241] A Ruano-Ravina A Figueiras M Freire-Garabal and J MBarros-Dios ldquoAntioxidant vitamins and risk of lung cancerrdquoCurrent Pharmaceutical Design vol 12 no 5 pp 599ndash613 2006

[242] D Albanes ldquoBeta-carotene and lung cancer a case studyrdquo TheAmerican Journal of Clinical Nutrition vol 69 no 6 pp 1345Sndash1350S 1999

[243] M L Neuhouser R E Patterson M D Thornquist G SOmenn I B King and G E Goodman ldquoFruits and vegetablesare associated with lower lung cancer risk only in the placeboarm of the 120573-Carotene and Retinol Efficacy Trial (CARET)rdquoCancer Epidemiology Biomarkers and Prevention vol 12 no 4pp 350ndash358 2003

[244] Y G J van Helden J Keijer A M Knaapen et al ldquoBeta-carotene metabolites enhance inflammation-induced oxidativeDNA damage in lung epithelial cellsrdquo Free Radical Biology andMedicine vol 46 no 2 pp 299ndash304 2009

[245] F McArdle L E Rhodes R A G Parslew et al ldquoEffects oforal vitamin E and 120573-carotene supplementation on ultravioletradiation-induced oxidative stress in human skinrdquo AmericanJournal of Clinical Nutrition vol 80 no 5 pp 1270ndash1275 2004

[246] CWolf A Steiner and H Honingsmann ldquoDo oral carotenoidsprotect human skin against ultraviolet erythema psoralenphototoxicity and ultraviolet-induced DNA-damagerdquo Journalof Investigative Dermatology vol 90 no 1 pp 55ndash57 1988

[247] M Garmyn J D Ribaya-Mercado RM Russel J Bhawan andB A Gilchrest ldquoEffect of beta-carotene supplementation on thehuman sunburn reactionrdquo Experimental Dermatology vol 4no 2 pp 104ndash111 1995

[248] P Korbashi R Kohen J Katzhendler and M Chevion ldquoIronmediates paraquat toxicity in Escherichia colirdquo The Journal ofBiological Chemistry vol 261 no 27 pp 12472ndash12476 1986

[249] R Kohen and M Chevion ldquoTransition metals potentiateparaquat toxicityrdquo Free radical research communications vol 1no 2 pp 79ndash88 1985

[250] C Latchoumycandane and P PMathur ldquoEffects of vitamin E onreactive oxygen species-mediated 2378-tetrachlorodibenzo-p-dioxin toxicity in rats testisrdquo Journal of Applied Toxicology vol22 no 5 pp 345ndash351 2002

[251] A Furukawa S Oikawa M Murata Y Hiraku and S Kawan-ishi ldquo(-)-Epigallocatechin gallate causes oxidative damage toisolated and cellular DNArdquo Biochemical Pharmacology vol 66no 9 pp 1769ndash1778 2003

[252] K Sakano S Oikawa Y Hiraku and S Kawanishi ldquoOxida-tive DNA damage induced by a melatonin metabolite 6-hydroxymelatonin via a unique non-o-quinone type of redoxcyclerdquo Biochemical Pharmacology vol 68 no 9 pp 1869ndash18782004

[253] B Poljsak D Suput and I Milisav ldquoAchieving the balancebetween ROS and antioxidants when to use the syntheticantioxidantsrdquo Oxidative Medicine and Cellular Longevity vol2013 Article ID 956792 11 pages 2013

[254] B Poljsak and I Milisav ldquoThe neglected significance of lsquoantiox-idative stressrsquordquo Oxidative Medicine and Cellular Longevity vol2012 Article ID 480895 12 pages 2012

[255] S Verhaegn J Adrain J McGovan A R Brophy R SFernandes and T G Gotler ldquoInhibition of apoptosis by antiox-idants in the human IIL-60 leukemia cell linerdquo BiochemicalPharmacology vol 40 pp 1021ndash1029 1995


[256] R I Salganik ldquoThe benefits and hazards of antioxidantscontrolling apoptosis and other protective mechanisms incancer patients and the human populationrdquo The Journal of theAmerican College of Nutrition vol 20 supplement 5 pp 464Sndash472S 2001

[257] I D Podmore H R Griffiths K E Herbert N Mistry P Mis-try and J Lunec ldquoVitamin C exhibits pro-oxidant propertiesrdquoNature vol 392 no 6676 p 559 1998

[258] P Palozza ldquoProoxidant actions of carotenoids in biologicsystemsrdquo Nutrition Reviews vol 56 no 9 pp 257ndash265 1998

[259] G S Omenn G E Goodman M D Thornquist et al ldquoEffectsof a combination of beta carotene and vitamin A on lungcancer and cardiovascular diseaserdquoThe New England Journal ofMedicine vol 334 no 18 pp 1150ndash1155 1996

[260] G Bjelakovic D Nikolova R G Simonetti and C GluudldquoAntioxidant supplements for prevention of gastrointestinalcancers a systematic review andmeta-analysisrdquoTheLancet vol364 no 9441 pp 1219ndash1228 2004

[261] E R Miller III R Pastor-Barriuso D Dalal R A RiemersmaL J Appel and E Guallar ldquoMeta-analysis high-dosage vitaminE supplementation may increase all-cause mortalityrdquo Annals ofInternal Medicine vol 142 no 1 pp 37ndash46 2005

[262] R G Cutler andM PMattson ldquoMeasuring oxidative stress andinterpreting its relevance in humansrdquo in Oxidative Stress andAging R G Cutler and H Rodriguez Eds World ScientificRiver Edge NJ USA 2003

[263] R G Cutler ldquoGenetic stability dysdifferentiation and longevitydeterminant genesrdquo in Critical Reviews of Oxidative Stress andDamage R G Cutler and H Rodriguez Eds World ScientificRiver Edge NJ USA 2003

[264] D W Filho S A Junior F P Possamai et al ldquoAntioxidanttherapy attenuates oxidative stress in the blood of subjectsexposed to occupational airborne contamination from coalmining extraction and incineration of hospital residuesrdquo Eco-toxicology vol 19 no 7 pp 1193ndash1200 2010

[265] ACherubini G BVignaG Zuliani C RuggieroU Senin andR Fellin ldquoRole of antioxidants in atherosclerosis epidemiolog-ical and clinical updaterdquo Current Pharmaceutical Design vol 11no 16 pp 2017ndash2032 2005

[266] S B Lotito and B Frei ldquoConsumption of flavonoid-rich foodsand increased plasma antioxidant capacity in humans causeconsequence or epiphenomenonrdquo Free Radical Biology ampMedicine vol 41 no 12 pp 1727ndash1746 2006

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


by individuals living in polluted areas or (ii) physiologicalprotection to increase the antioxidative defence of the organ-ism There is growing scientific evidence that low molecular-weight antioxidants are involved in the prevention of or thedecrease in the damage caused by certain environmentalpollutants Because we have little influence on the increasinglevels of endogenous antioxidants it would be reasonableto increase the amount of exogenous antioxidants (mainlythrough ingestion) to strengthen the defensive propertiesof organisms against environmental oxidative stress Thecurrent evidence suggests that increased consumption offruits and vegetables or certain dietary supplements cansubstantially enhance the protection against many commontypes of environmentally induced ONS

2 Purpose

This review aims to determine whether antioxidants canmodulate the toxicity of environmental pollutants therebyinfluencing health and disease outcome associated withoxidative stress-induced insults Evidence will be presentedthat environmental pollution increases oxidative stress andthat dietary supplementation with antioxidants may playa role on the neutralization or buffering of the effects ofpollutants with oxidizing properties The recommendationfor the use of dietary antioxidants in areas of increasedenvironmental pollution will be discussed

This review summarises the most common and health-relevant sources of oxidative stress like air pollution radia-tion pesticides noise and household chemicals Due to spaceconstrains and a broad scientific data not all the studiescould be covered in this reviewThe reader is thus referred tosearch through provided references (and references therein)for further details on selected environmental pollutant orselected antioxidant

21 Air Pollution-Induced Oxidative Stress and Protectionagainst It The health effects of air pollution result fromminor irritation of the eyes and the upper respiratory systemto chronic respiratory disease heart and vascular diseaselung cancer and death Different studies presented in Table 1are demonstrating increased oxidative stressdamage dueto air pollutant exposure and that antioxidants could offercertain level of protection [4ndash7]

Oxygen could be presented as the leading air pollutantin regard to oxidative stress formation Molecular O

2

itselfqualifies as a free radical because it has twounpaired electronswith parallel spin in different 120587-antibonding orbitals Thisspin restriction accounts for its relative stability and paramag-netic properties O

2

is capable of accepting electrons to itsantibonding orbitals becoming ldquoreducedrdquo in the process andtherefore functioning as a strong oxidizing agent [76] Thediatomic molecule of oxygen contains two uncoupled elec-trons and can therefore undergo reduction yielding severaldifferent oxygen metabolites which are collectively calledROS Mitochondria are the main site of intracellular oxygenconsumption and the main source of ROS formation [8 1013 77] Once ROS are produced they are removed by cellular

defenses which include the enzymes superoxide dismutase(Mn-SOD CuZn-SOD and extracellular (EC)-SOD) cata-lase glutathione peroxidase peroxiredoxins and the nonen-zymatic antioxidants like glutathione (GSH) thiore-doxinascorbate 120572-tocopherol and uric acid [9 78] Since oxidativedamage of cells increases with age the increased intakeof exogenous antioxidants may support the endogenousantioxidative defense Clinical studies imply that eating a dietrich in fruits vegetables whole grains legumes and omega-3fatty acids can help humans in decreasing oxidative stress andpostponing the incidence of degenerative diseases [79]

Ozone is formed from dioxygen by the action of ultra-violet light and atmospheric electrical discharges Ozone isa very reactive gas whose uptake depends on the availabilityof antioxidants in the lining fluids [17 18 52] The surface ofthe lung is covered with a thin layer of fluid that containsa range of antioxidants that appear to provide the first lineof defence against air pollutants Mudway et al [17] studiedthe interaction of ozone with antioxidants and found that thehierarchy toward ozone in human epithelial lining fluid wasascorbic acid followed by uric acid and then glutathione Wuand Meng [34] analysed the effects of sea buckthorn seed oilon the protection against sulphur dioxide inhalation Theyfound that buckthorn seed oil contributed antioxidant effectsFurthermore study by Zhao et al [33] revealed the protectiveeffect of salicylic acid and vitamin C on sulphur dioxide-induced lipid peroxidation in mice

Tobacco smoke is one of the most common air pollutantsand generates high amounts of various ROSRNS Cigarette-induced oxidative stress was found to be affected by theprotective effects of vitamin C glutathione and other antiox-idants mainly as quenchers of ROSRNS (Table 1) [36ndash41]

Kienast et al [54] demonstrated that alveolar macro-phages and peripheral blood mononuclear cells become acti-vated following exposure to nitrogen dioxide Several studieshave demonstrated that certain antioxidants might play abeneficial role in NO

119909

-induced toxicity Guth and Mavis [55]and Sevanian et al [56 80] examined the effect of vitaminE content on the lungs Furthermore a study by Bohm et al[62] revealed that dietary uptake of tomato lycopene protectshuman cells against nitrogen dioxide-mediated damage Thepossible influence of dietary antioxidants especially vitaminC on the increasing prevalence of asthma was explored byHatch [81]

Particulate matter can also cause oxidative stress viadirect generation of ROS from the surfaces of soluble com-pounds altering the function of mitochondria or reducingthe activity of nicotinamide adenine dinucleotide phosphate-oxidase inducing the activation of inflammatory cells to gen-erate ROS and RNS and mediating oxidative DNA damage[63 82] Antioxidants could also provide protection againstparticulate matter-induced toxicity Indeed lung lining fluidantioxidants (urate glutathione and ascorbate) were demon-strated to be effective in a study by Greenwell et al [83] Luoet al [70] detected an inhibitory effect of green tea extract onthe carcinogenesis induced by the combination of asbestosand benzo(a)pyrene in rats drinking 2 green tea extractthroughout their lives




Oxygen (O2)








Ozone (O3)














Cigarettesmoke















Table 1 Continued


Nitrogenoxides (NO

119909

)















Asbestos














Table2Stud

iesd

emon

stratin


tressdam

aged

ueto

ionisin

gandno

nion

ising

radiationexpo

sure

andthep

rotectivee

ffectso

fantioxidants

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

Ionisin

gradiation

8-OHdG

Speratietal(19

99)[84]

Ebselen

TakandPark

(200

9)[85]

ROSsuperoxide

(O2

∙minus

)and

the


)N-acetylcysteine

Kilciksiz

etal(20082011)

[8687]

DNAdamagea

ndlip

idmem

brane

damage

Quercetin

andthee

thanolicextracto

fprop

olis

Benk

ovicetal(2009)[88]

L-seleno

methion

inevitamin

Cvitamin

Esuccinatethec

ombinatio

nof

alph

a-lip

oica


Wam

bietal(2009)[97]

And

rade

etal(2011)[98]

Curcum

inJagetia

(2007)

[89]

Sesamol

GG

Naira

ndC

KK

Nair

(2010)

[99]

Melaton

invitamin

E

El-M

issiry

etal(2007)[100]

Karbow

nikandRe

iter(2000)

[101]

Lycopene

Naire

tal(2003)

[102]

Noaman

etal(2002)[103]

Berbee

etal(200

9)[104]

Green

teap

olypheno

lsSrinivasan

etal(2009)[105]

Huetal(2011)[106]

Non

ionisin

gradiation

ROSprod

uctio

nKo

vacica

ndSomanathan(2010)

[90]

Alpha-to

coph

erol

Wolfetal(2005)

[107]

Simko

andMattss

on(200

4)[91]

N-acetyl-L

-cysteinea


Guler

etal(2008)[108]

Ozgur

etal(2010)[109]


Enhanced

lipid

peroxidatio

nand

alteredantio

xidant

defences

ystems

Simko

(2007)

[110]

Mela

toninandcaffeicacid

phenethyl

ester

Ozgun

eretal(2006)[93]

Jajte

etal(2001)[94]

Reiter(1994)[111]

DNAdamage

Jajte

etal(2001)[94]

Ginkgo

biloba

Ilhan

etal(2004

)[95]

L-carnitine

andselenium

Naziro

gluandGum

ral(2009)

[112]

VitaminsE

andC

Gun

eyetal(2007)

[96]


Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2


superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]


lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno


oflutein

andlycopene


Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]







2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Oxygen (O2)








Ozone (O3)














Cigarettesmoke















Table 1 Continued


Nitrogenoxides (NO

119909

)















Asbestos














Table2Stud

iesd

emon

stratin


tressdam

aged

ueto

ionisin

gandno

nion

ising

radiationexpo

sure

andthep

rotectivee

ffectso

fantioxidants

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

Ionisin

gradiation

8-OHdG

Speratietal(19

99)[84]

Ebselen

TakandPark

(200

9)[85]

ROSsuperoxide

(O2

∙minus

)and

the


)N-acetylcysteine

Kilciksiz

etal(20082011)

[8687]

DNAdamagea

ndlip

idmem

brane

damage

Quercetin

andthee

thanolicextracto

fprop

olis

Benk

ovicetal(2009)[88]

L-seleno

methion

inevitamin

Cvitamin

Esuccinatethec

ombinatio

nof

alph

a-lip

oica


Wam

bietal(2009)[97]

And

rade

etal(2011)[98]

Curcum

inJagetia

(2007)

[89]

Sesamol

GG

Naira

ndC

KK

Nair

(2010)

[99]

Melaton

invitamin

E

El-M

issiry

etal(2007)[100]

Karbow

nikandRe

iter(2000)

[101]

Lycopene

Naire

tal(2003)

[102]

Noaman

etal(2002)[103]

Berbee

etal(200

9)[104]

Green

teap

olypheno

lsSrinivasan

etal(2009)[105]

Huetal(2011)[106]

Non

ionisin

gradiation

ROSprod

uctio

nKo

vacica

ndSomanathan(2010)

[90]

Alpha-to

coph

erol

Wolfetal(2005)

[107]

Simko

andMattss

on(200

4)[91]

N-acetyl-L

-cysteinea


Guler

etal(2008)[108]

Ozgur

etal(2010)[109]


Enhanced

lipid

peroxidatio

nand

alteredantio

xidant

defences

ystems

Simko

(2007)

[110]

Mela

toninandcaffeicacid

phenethyl

ester

Ozgun

eretal(2006)[93]

Jajte

etal(2001)[94]

Reiter(1994)[111]

DNAdamage

Jajte

etal(2001)[94]

Ginkgo

biloba

Ilhan

etal(2004

)[95]

L-carnitine

andselenium

Naziro

gluandGum

ral(2009)

[112]

VitaminsE

andC

Gun

eyetal(2007)

[96]


Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2


superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]


lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno


oflutein

andlycopene


Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]







2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table 1 Continued


Nitrogenoxides (NO

119909

)















Asbestos














Table2Stud

iesd

emon

stratin


tressdam

aged

ueto

ionisin

gandno

nion

ising

radiationexpo

sure

andthep

rotectivee

ffectso

fantioxidants

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

Ionisin

gradiation

8-OHdG

Speratietal(19

99)[84]

Ebselen

TakandPark

(200

9)[85]

ROSsuperoxide

(O2

∙minus

)and

the


)N-acetylcysteine

Kilciksiz

etal(20082011)

[8687]

DNAdamagea

ndlip

idmem

brane

damage

Quercetin

andthee

thanolicextracto

fprop

olis

Benk

ovicetal(2009)[88]

L-seleno

methion

inevitamin

Cvitamin

Esuccinatethec

ombinatio

nof

alph

a-lip

oica


Wam

bietal(2009)[97]

And

rade

etal(2011)[98]

Curcum

inJagetia

(2007)

[89]

Sesamol

GG

Naira

ndC

KK

Nair

(2010)

[99]

Melaton

invitamin

E

El-M

issiry

etal(2007)[100]

Karbow

nikandRe

iter(2000)

[101]

Lycopene

Naire

tal(2003)

[102]

Noaman

etal(2002)[103]

Berbee

etal(200

9)[104]

Green

teap

olypheno

lsSrinivasan

etal(2009)[105]

Huetal(2011)[106]

Non

ionisin

gradiation

ROSprod

uctio

nKo

vacica

ndSomanathan(2010)

[90]

Alpha-to

coph

erol

Wolfetal(2005)

[107]

Simko

andMattss

on(200

4)[91]

N-acetyl-L

-cysteinea


Guler

etal(2008)[108]

Ozgur

etal(2010)[109]


Enhanced

lipid

peroxidatio

nand

alteredantio

xidant

defences

ystems

Simko

(2007)

[110]

Mela

toninandcaffeicacid

phenethyl

ester

Ozgun

eretal(2006)[93]

Jajte

etal(2001)[94]

Reiter(1994)[111]

DNAdamage

Jajte

etal(2001)[94]

Ginkgo

biloba

Ilhan

etal(2004

)[95]

L-carnitine

andselenium

Naziro

gluandGum

ral(2009)

[112]

VitaminsE

andC

Gun

eyetal(2007)

[96]


Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2


superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]


lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno


oflutein

andlycopene


Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]







2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Stud

iesd

emon

stratin


tressdam

aged

ueto

ionisin

gandno

nion

ising

radiationexpo

sure

andthep

rotectivee

ffectso

fantioxidants

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

Ionisin

gradiation

8-OHdG

Speratietal(19

99)[84]

Ebselen

TakandPark

(200

9)[85]

ROSsuperoxide

(O2

∙minus

)and

the


)N-acetylcysteine

Kilciksiz

etal(20082011)

[8687]

DNAdamagea

ndlip

idmem

brane

damage

Quercetin

andthee

thanolicextracto

fprop

olis

Benk

ovicetal(2009)[88]

L-seleno

methion

inevitamin

Cvitamin

Esuccinatethec

ombinatio

nof

alph

a-lip

oica


Wam

bietal(2009)[97]

And

rade

etal(2011)[98]

Curcum

inJagetia

(2007)

[89]

Sesamol

GG

Naira

ndC

KK

Nair

(2010)

[99]

Melaton

invitamin

E

El-M

issiry

etal(2007)[100]

Karbow

nikandRe

iter(2000)

[101]

Lycopene

Naire

tal(2003)

[102]

Noaman

etal(2002)[103]

Berbee

etal(200

9)[104]

Green

teap

olypheno

lsSrinivasan

etal(2009)[105]

Huetal(2011)[106]

Non

ionisin

gradiation

ROSprod

uctio

nKo

vacica

ndSomanathan(2010)

[90]

Alpha-to

coph

erol

Wolfetal(2005)

[107]

Simko

andMattss

on(200

4)[91]

N-acetyl-L

-cysteinea


Guler

etal(2008)[108]

Ozgur

etal(2010)[109]


Enhanced

lipid

peroxidatio

nand

alteredantio

xidant

defences

ystems

Simko

(2007)

[110]

Mela

toninandcaffeicacid

phenethyl

ester

Ozgun

eretal(2006)[93]

Jajte

etal(2001)[94]

Reiter(1994)[111]

DNAdamage

Jajte

etal(2001)[94]

Ginkgo

biloba

Ilhan

etal(2004

)[95]

L-carnitine

andselenium

Naziro

gluandGum

ral(2009)

[112]

VitaminsE

andC

Gun

eyetal(2007)

[96]


Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2


superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]


lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno


oflutein

andlycopene


Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]







2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Radiation

Increasedoxidatives

tressmarkers

Stud

yAntioxidantse

xertingap

rotectivee

ffect

Stud

y

UVR

Generationof

oxidantsvia

photod

ynam

icactio

n(egH

2O2


superoxide

anion

andhydroxyl

radicals)

Peak

etal(1988)[113]

Beehlere

tal(19

92)[114

]Be

rton

etal(1997)[115]

Lietal(1996)[116

]Masaki(2010)[117

]

Vitamin

CMcA

rdleetal(2002)[118

]Hum

bertetal(2003)[119

]

Tocoph

erol

Ritte

retal(1997)

[120]

Packer

etal(2001)[121]

Stahletal(200

0)[122]


lar

DNA

JHK

ligman

andAM

Kligman

(1986)

[123]

Vitamin

Abeta-caroteneand

other

caroteno

ids

Stahletal(200

6)[124]

Sies

andStahl(2004)[125]

Choetal(2010)[126]

Stahletal(200

0)[122]

Photoaging

McA

rdleetal(2002)[118

]Sh

indo

etal(1993)[127]

Packer

andVa

lacchi

(2002)

[128]

Depletio

nof

antio

xidants

Thiele(2001)[129]

Ribaya-M

ercado

etal(1995)[130]

Caroteno


oflutein

andlycopene


Leee

tal(200

0)[132]

Stahletal(1998)

[133]

Lycopene

Stahletal(1998)

[133]

Austetal(2005)[134]

Yehetal(2005)[135]

Resveratrol

AfaqandMuk

htar

(2002)

[136]

Green

teap

olypheno

lsandother

flavono

ids

Katiy

aretal(2000)[137]

Katiy

ar(2003)

[138]

Katiy

aretal(2010)[139]

Luetal(2008)

[140]

Sing

handAgarw

al(2002)

[141]

Bonina

etal(1996)[142]

Weietal(1995)[143]

Pycnogenol

Salio

uetal(2001)[144]







2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















2

∙minus and H2

O2







General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















General




Yi et al (2007) [167]









Aono et al (1995) [173]







Aldrin anddieldrin




















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table 3 Continued











Zhu et al (2009) [155]







































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of










































2


2


2

O2

to form singlet O2


2













3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























3








UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















UVR
















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















3 Conclusions







References































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































2
































































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




























































































2

O2






































































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



























































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Review Article The Protective Role of Antioxidants in the...

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