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An overview of Antioxidants in healthcare - Usesand Estimation
Submitted byrajaon Mon, 10/27/2008 - 20:31
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Kushal H.Sanghvi
An Antioxidant is a molecule capable of slowing or preventing the oxidation of other
molecules. Oxidation is a chemical reaction that transfers electrons from a substanceto an oxidizing agent. Oxidation reactions can produce free radicals, which start chain
reactions that damage cells. Antioxidants terminate these chain reactions by
removing radical intermediates, and inhibit other oxidation reactions by being
oxidized themselves. As a result, antioxidants are often reducing agents such as thiols
or polyphenols.[1]
Although oxidation reactions are crucial for life, they can also be damaging; hence,
plants and animals maintain complex systems of multiple types of antioxidants, such
as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase,
superoxide dismutase and various peroxidases. Low levels of antioxidants, orinhibition of the antioxidant enzymes causes oxidative stress and may damage or kill
cells.
As oxidative stress[7] has been associated with the pathogenesis of many human
diseases, the use of antioxidants in pharmacology is intensively studied, particularly
as treatments for stroke and neurodegenerative diseases. However, it is unknown
whether oxidative stress is the cause or the consequence of such diseases.
Antioxidants are also widely used as ingredients in dietary supplements in the hope of
maintaining health and preventing diseases such as cancer and coronary heart
disease. Although some studies have suggested antioxidant supplements have healthbenefits, other large clinical trials did not detect any benefit for the formulations
tested, and excess supplementation may occasionally be harmful. In addition to these
uses in medicine, antioxidants have many industrial uses, such as preservatives in
food and cosmetics and preventing the degradation of rubber and gasoline.
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Space-filling model of the antioxidant metabolite glutathione.
The yellow sphere is the redox-active sulfur atom that provides antioxidant activity,
while the red, blue, white, and dark grey spheres represent oxygen, nitrogen,
hydrogen, and carbon atoms, respectively.
The oxidative challenge in biology
A paradox in metabolism is that while the vast majority of complex life requires
oxygen for its existence, oxygen is a highly reactive molecule that damages living
organisms by producing reactive oxygen species.Consequently, organisms contain a
complex network of antioxidant metabolites and enzymes that work together to
prevent oxidative damage to cellular components such as DNA, proteins and lipids.In
general, antioxidant systems either prevent these reactive species from being formed,
or remove them before they can damage vital components of the cell.[13].
The reactive oxygen species produced in cells include hydrogen peroxide (H2O2),
hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (OH) and the
superoxide anion (O2-). The hydroxyl radical is particularly unstable and will react
rapidly and non-specifically with most biological molecules. This species is produced
from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton
reaction. These oxidants can damage cells by starting chemical chain reactions such
as lipid peroxidation, or by oxidizing DNA or proteins.
Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA
repair mechanisms, while damage to proteins causes enzyme inhibition, denaturation
and protein degradation.
The use of oxygen as part of the process for generating metabolic energy produces
reactive oxygen species.In this process, the superoxide anion is produced as a by-
product of several steps in the electron transport chain.Particularly important is thereduction of coenzyme Q[14] in complex III, since a highly reactive free radical is
formed as an intermediate (Q-). This unstato electron "leakage" when electrons jump
directly to molecular oxygen and form the superoxide anion, instead of moving
through the series of well-controlled reactions of the electron transport chain. In a
similar set of reactions in plants, reactive oxygen species are also produced during
photosynthesis under conditions of high light intensity.
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The structure of the antioxidant vitamin ascorbic acid (vitamin C).
Metabolites
Overview
Antioxidants are classified into two broad divisions, depending on whether they are
soluble in water (hydrophilic) or in lipids (hydrophobic). In general, water-soluble
antioxidants react with oxidants in the cell cytoplasm and the blood plasma, while
lipid-soluble antioxidants protect cell membranes from lipid peroxidation. These
compounds may be synthesized in the body or obtained from the diet.The different
antioxidants are present at a wide range of concentrations in body fluids and tissues,
with some such as glutathione or ubiquinone mostly present within cells, while others
such as uric acid are more evenly distributed throughout the body.
The relative importance and interactions between these different antioxidants is a
complex area, with the various metabolites and enzyme systems having synergistic
and interdependent effects on one another. The action of one antioxidant may
depend on the proper function of other members of the antioxidant system. The
amount of protection provided by any one antioxidant therefore depends on its
concentration, its reactivity towards the particular reactive oxygen species being
considered, and the status of the antioxidants with which it interacts.
Some compounds contribute to antioxidant defense by chelating transition metals and
preventing them from catalyzing the production of free radicals in the cell.
Particularly important is the ability to sequester iron, which is the function of iron-
binding proteins such as transferrin and ferritin.Selenium and zinc are commonly
referred to as antioxidant nutrients, but these chemical elements have no antioxidant
action themselves and are instead required for the activity of some antioxidant
enzymes, as is discussed below.
Antioxidant metabolite SolubilityConcentration in human serum
(M)
Concentration in liver tissue
(mol/kg)
Ascorbic acid(vitaminC)
Water 50 60 260 (human)
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Glutathione Water 325 650 6,400 (human)
Lipoic acid Water 0.1 0.7 4 5 (rat)
Uric acid Water 200 400 1,600 (human)
Carotenes Lipid-carotene: 0.5 1
retinol(vitamin A): 1 35 (human, total carotenoids)
-tocopherol(vitamin E) Lipid 10 40 50 (human)
Ubiquinol(coenzyme Q) Lipid 5 200 (human)
Ascorbic acid
(Vitamin-C)
Ascorbic acid or "vitamin C"[3],[29] is a monosaccharide antioxidant found in both
animals and plants. As it cannot be synthesised in humans and must be obtained from
the diet, it is a vitamin. Most other animals are able to produce this compound in
their bodies and do not require it in their diets. In cells, it is maintained in its
reduced form by reaction with glutathione, which can be catalysed by protein
disulfide isomerase and glutaredoxins. Ascorbic acid is a reducing agent and can
reduce and thereby neutralize reactive oxygen species such as hydrogen peroxide. In
addition to its direct antioxidant effects, ascorbic acid is also a that is particularly
important in stress resistance in plants.
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Glutathione
The free radical mechanism of lipid peroxidation.Glutathione is a cysteine-containing
peptide found in most forms of aerobic life.It is not required in the diet and is instead
synthesized in cells from its constituent amino acids.Glutathione has antioxidant
properties since the thiol group in its cysteine moiety is a reducing agent and can bereversibly oxidized and reduced. In cells, glutathione is maintained in the reduced
form by the enzyme glutathione reductase and in turn reduces other metabolites and
enzyme systems as well as reacting directly with oxidants. Due to its high
concentration and its central role in maintaining the cell's redox state, glutathione is
one of the most important cellular antioxidants.[34],[15].
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Melatonin
Melatonin is a powerful antioxidant that can easily cross cell membranes and the
blood-brain barrier. Unlike other antioxidants, melatonin does not undergo redox
cycling, which is the ability of a molecule to undergo repeated reduction and
oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act aspro-oxidants and promote free radical formation. Melatonin, once oxidized, cannot be
reduced to its former state because it forms several stable end-products upon
reacting with free radicals. Therefore, it has been referred to as a terminal (or
suicidal) antioxidant.[16].
Tocopherols and tocotrienols (Vitamin-E)
Vitamin E is the collective name for a set of eight related tocopherols and
tocotrienols, which are fat-soluble antioxidant vitamins. Of these, a-tocopherol hasbeen most studied as it has the highest bioavailability, with the body preferentially
absorbing and metabolising this form.
The a-tocopherol form is the most important lipid-soluble antioxidant and protects
cell membranes against oxidation by reacting with the lipid radicals produced in the
lipid peroxidation chain reaction. This removes the free radical intermediates and
prevents the propagation reaction from continuing. The oxidised a-tocopheroxyl
radicals produced in this process may be recycled back to the active reduced form
through reduction by ascorbate, retinol or ubiquinol.
The functions of the other forms of vitamin E are less well-studied, although ?-
tocopherol is a nucleophile that may react with electrophilic mutagens, and
tocotrienols may have a specialised role in neuroprotection.[17],[18].
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The free radical mechanism oflipid peroxidation.
Pro-oxidant activities
Antioxidants that are reducing agents can also act as pro-oxidants. For example,
vitamin C has antioxidant activity when it reduces oxidizing substances such as
hydrogen peroxide, however, it can also reduce metal ions which leads to thegeneration of free radicals through the Fenton reaction.[8],[23].
2 Fe3++ Ascorbate 2 Fe2+ + Dehydroascorbate
2 Fe2++ 2 H2O2 2 Fe3+ + 2 OH + 2 OH-
The relative importance of the antioxidant and pro-oxidant activities of antioxidants
are an area of current research, but vitamin C, for example, appears to have a mostly
antioxidant action in the body. However, less data is available for other dietary
antioxidants, such as polyphenol antioxidants, zinc, and vitamin E.[23].
Dietary Antioxidants
A substance in food that significantly decreses the adverse effects of reactive
species,such as reactlive oxygen and nitrogen species,on normal physiological
functions in humans.
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Reactive Species Includes:
Hydroxyl radicals (.OH), Superoxideanions (O2-), Singlet oxygen(1O2), Hydrogenperoxides (H2O2), Organic peroxides (R-OOH), Nitric oxide, Peroxynitrite
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Diversity in Dietary Antioxidants
Essential
Vitamin E (tocopherol)
Vitamin C (ascorbic acid)
Vitamin A (retinol andcarotenoids)
Numerous minerals-Cu, Mn, Zn, Se, Fe
Non-essential
Glutathione
small peptides
host ofphytochemicals(thousands in food supply)
Enzymatic pathway for detoxification of reactive oxygen species.Overview
As with the chemical antioxidants, cells are protected against oxidative stress by an
interacting network of antioxidant enzymes. Here, the superoxide released by
processes such as oxidative phosphorylation is first converted to hydrogen peroxide
and then further reduced to give water. This detoxification pathway is the result of
multiple enzymes, with superoxide dismutases catalysing the first step and then
catalases and various peroxidases removing hydrogen peroxide. As with antioxidant
metabolites, the contributions of these enzymes can be hard to separate from one
another, but the generation of transgenic mice lacking just one antioxidant enzymecan be informative.[13],[7].
Superoxide dismutase, catalase and peroxiredoxins
Superoxide dismutases (SODs) are a class of closely related enzymes that catalyse the
breakdown of the superoxide anion into oxygen and hydrogen peroxide. SOD enzymes
are present in almost all aerobic cells and in extracellular fluids. Superoxide
dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can
be copper, zinc, manganese or iron. In humans, the copper/zinc SOD is present in the
cytosol, while manganese SOD is present in the mitochondrion. There also exists a
third form of SOD in extracellular fluids, which contains copper and zinc in its active
sites. The mitochondrial isozyme seems to be the most biologically important of these
three, since mice lacking this enzyme die soon after birth. In contrast, the mice
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lacking copper/zinc SOD are viable but have lowered fertility, while mice without the
extracellular SOD have minimal defects. In plants, SOD isozymes are present in the
cytosol and mitochondria, with an iron SOD found in chloroplasts that is absent from
vertebrates and yeast.[19],[20].
Catalases are enzymes that catalyse the conversion of hydrogen peroxide to waterand oxygen, using either an iron or manganese cofactor. This protein is localized to
peroxisomes in most eukaryotic cells.
Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate,
it follows a ping-pong mechanism. Here, its cofactor is oxidised by one molecule of
hydrogen peroxide and then regenerated by transferring the bound oxygen to a
second molecule of substrate. Despite its apparent importance in hydrogen peroxide
removal, humans with genetic deficiency of catalase "acatalasemia" or mice
genetically engineered to lack catalase completely, suffer few ill effects.[20].
Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide,
organic hydroperoxides, as well as peroxynitrite. They are divided into three classes:
typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine
peroxiredoxins. These enzymes share the same basic catalytic mechanism, in which a
redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a
sulfenic acid by the peroxide substrate. Peroxiredoxins seem to be important in
antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan
and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove
hydrogen peroxide generated in chloroplasts.
Thioredoxin and glutathione systems
The thioredoxin system contains the 12-kDa protein thioredoxin and its companion
thioredoxin reductase. Proteins related to thioredoxin are present in all sequenced
organisms, with plants such as Arabidopsis thaliana having a particularly great
diversity of isoforms. The active site of thioredoxin consists of two neighboring
cysteines, as part of a highly-conserved CXXC motif, that can cycle between an active
dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin
acts as an efficient reducing agent, scavenging reactive oxygen species and
maintaining other proteins in their reduced state.After being oxidized, the active
thioredoxin is regenerated by .[22].
The glutathione system includes glutathione, glutathione reductase, glutathione
peroxidases and glutathione S-transferases.This system is found in animals, plants and
microorganisms. Glutathione peroxidase is an enzyme containing four selenium-
cofactors that catalyzes the breakdown of hydrogen peroxide and organic
hydroperoxides. There are at least four different glutathione peroxidase isozymes in
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animals. Glutathione peroxidase 1 is the most abundant and is a very efficient
scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with
lipid hydroperoxides.
Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme
have normal lifespans. but they are hypersensitive to induced oxidative stress. Inaddition, the glutathione S-transferases are another class of glutathione-dependent
antioxidant enzymes that show high activity with lipid peroxides. These enzymes are
at particularly high levels in the liver and also serve in detoxification metabolism.
Decameric structure of AhpC, a bacterial 2-
cysteine peroxiredoxin fromSalmonella typhimurium.
Role In Diseases
Oxidative stress in disease
Oxidative stress is thought to contribute to the development of a wide range of
diseases including Alzheimer's disease, Parkinson's disease, the pathologies caused by
diabetes., rheumatoid arthritis, and neurodegeneration in motor neurone diseases. In
many of these cases, it is unclear if oxidants trigger the disease, or if they are
produced as a consequence of the disease and cause the disease symptoms; as a
plausible alternative, a neurodegenerative disease might result from defective axonal
transport of mitochondria, which carry out oxidation reactions. One case in which thislink is particularly well-understood is the role of oxidative stress in cardiovascular
disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process
of atherogenesis, which results in atherosclerosis, and finally cardiovascular
disease.[27].
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A low calorie diet extends median and maximum lifespan in many animals. This effect
may involve a reduction in oxidative stress. While there is good evidence to support
the role of oxidative stress in aging in model organisms such as Drosophila
melanogaster and Caenorhabditis elegans, the evidence in mammals is less clear.
Diets high in fruit and vegetables, which are high in antioxidants, promote health andreduce the effects of ageing, however antioxidant vitamin supplementation has no
detectable effect on the ageing process, so the effects of fruit and vegetables may be
unrelated to their antioxidant contents.[7][11].
Measurement and levels in food
Fruits and vegetables are good sources of antioxidants. Measurement of antioxidants
is not a straightforward process, as this is a diverse group of compounds with different
reactivities to different reactive oxygen species. In food science, the oxygen radical
absorbance capacity (ORAC) has become the current industry standard for assessing
antioxidant strength of whole foods, juices and food additives.Other measurement
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tests include the Folin-Ciocalteu reagent, and the trolox equivalent antioxidant
capacity assay. In medicine, a range of different assays are used to assess the
antioxidant capability of blood plasma and of these, the ORAC assay may be the most
reliable.[4][9][25].
Antioxidants are found in varying amounts in foods such as vegetables, fruits, graincereals, legumes and nuts. Some antioxidants such as lycopene and ascorbic acid can
be destroyed by long-term storage or prolonged cooking. Other antioxidant
compounds are more stable, such as the polyphenolic antioxidants in foods such as
whole-wheat cereals and tea. In general, processed foods contain less antioxidants
than fresh and uncooked foods, since the preparation processes may expose the food
to oxygen.
Antioxidant compounds Foods containing high levels of these antioxidants
Vitamin C (ascorbic acid) Fruitsandvegetables
Vitamin E (tocopherols,tocotrienols) Vegetable oils
Polyphenolic antioxidants (resveratrol,flavonoids) Tea,coffee,soy, fruit ,chocolate,oreganoandred
Carotenoids(lycopene,carotenes) Fruitandvegetables
Some antioxidants are made in the body and are not absorbed from the intestine. One
example is glutathione, which is made from amino acids. As any glutathione in the gut
is broken down to free cysteine, glycine and glutamic acid before being absorbed,
even large oral doses have little effect on the concentration of glutathione in the
body. Ubiquinol (coenzyme Q) is also poorly absorbed from the gut and is made inhumans through the mevalonate pathway.[17][18][29]
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Fruits and vegetables are good sources of antioxidants.
A list of some Antioxidants found in Food
Bilberries
Bilberries are rich in flavonoids - antioxidant nutrients which may help to protect the
body's cells from damage by excess free radicals.
CarnosineCarnosine is a multi-potent super-antioxidant which stabilizes and protects the cell
membrane. Specifically, as a water-soluble free radical scavenger it prevents lipid
peroxidation within the cell membrane. Many antioxidants (like vitamins E and C) are
aimed at preventing free radicals from entering the tissues, but have no effect after
this first line of defense is broken. Free radicals cause oxidative stress in the
body.Carnosine is not only effective in prevention, but it is also active after free
radicals react to form other dangerous compounds, like lipid peroxides and and
secondary products. So, it protects the tissues from these damaging 'second-wave'
chemicals.Carotenoids
Carotenoids are perhaps best known for their ability to be converted to vitamin A,
which is essential for healthy vision and reproduction, and for maintaining body
tissues. Carotenoids are also powerful antioxidants on their own right.
Co-Enzyme Q10
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Co Q10 is involved in the body's metabolic processes, particularly in the release of
energy from food. It is also a potent antioxidant. Antioxidants can mop up damaging
chemicals (free radicals) in the body and guard against many chronic diseases,
especially in the heart.[14]
Green Tea
Green tea is an excellent source of potent polyphenols, a strong antioxidant and
inhibitor of harmful Angiogenesis.
Vitamin A
Vitamin A, is a fat-soluble vitamin and is involved in the formation and maintenance
of healthy skin, hair, and mucous membranes. Vitamin A helps us to see in dim light
and is necessary for proper bone growth, tooth development, and fertility and has
been well documented for decades. It is also an important antioxidant.
Selenium
Doctors have dismissed the mineral as humbug, while others recommend it as a
valuable component in preventative medicine, or even prescribe it as part of a course
of treatment. Veterinary surgeons, on the other hand, have been using adjunct
selenium therapy for many years.[28][22]
Soy & Isoflavones Research suggests that soy may offer a number of health benefits
related to:
menopause symptom relief
osteoporosis
cardiovascular disease
immunity
cancer
Zinc
Zinc is vital to about 200 different enzymes, to the formation of bone tissue, in the
healing of wounds and sores, to the production of proteins, the regulation of
ribosomal, ribonucleic acid synthesis and insulin and in the carbohydrate metabolism.Zinc is also an antioxidant.[28]
Antioxidants a key to 'long life'
Boosting the body's levels of natural antioxidants could be the key to a long life,
according to US scientists.Mice engineered to produce high levels of an antioxidant
enzyme lived 20% longer and had less heart and other age-related diseases, they
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found.If the same is true in humans, people could live beyond 100 years.The
University of Washington work in Science Express backs the idea that high reactive
oxygen molecules, called free-radicals, cause ageing.
Long life
Free-radicals have been linked with heart disease, cancer and other age-related
diseases.Dr Peter Rabinovitch and colleagues bred mice that over-expressed the
enzyme catalase.By intervening in the underlying ageing process, we may be able to
produce very significant increases in healthy lifespan .Catalase acts as an antioxidant
by removing damaging hydrogen peroxide, which is a waste product of metabolism
and is a source of free-radicals.Free radical damage can lead to more flaws in the
cell's chemical processes and more free radicals, making a vicious cycle.
Antioxidant therapies for cystic fibrosis (CF).
Antioxidants may have a role in the slowing or prevention of CF lung disease. Ahealthy diet, including fruit and vegetables supplemented by fat-soluble vitamins, can
boost the CF patients antioxidant protection. However, in people with CF, the
digestion does not always guarantee proper nourishment since mucus tends to clog
the pancreas. Therefore, researchers are looking for alternative ways to deliver
antioxidants to CF patients. One compelling strategy is to supplement the fat-soluble
vitamins A, D, E and K. Another strategy is to administer oral N-acetylcysteine, or
NAC, which is a building block for the antioxidant glutathione.[34]
Coenzyme Q10 as an antioxidant
A substance found in most tissues in the body, and in many foods. It can also be madein the laboratory. It is used by the body to produce energy for cells, and as an
antioxidant. It is being studied in the treatment of cancer and in the relief of side
effects caused by some cancer treatments. Also called Q10, CoQ10, vitamin Q10, and
ubiquinone.[14].
Coenzyme Q 10 is a compound that is made naturally in the body. The body uses it for
cell growth and to protect cells from damage that could lead to cancer.Animal studies
have shown that coenzyme Q10 helps the immune system work better and makes the
body better able to resist certain infections and types of cancer.Clinical trials have
shown that coenzyme Q10 helps protect the heart from the damaging side effects ofdoxorubicin, a drug used to treat cancer.In 3 small studies of coenzyme Q10 in breast
cancer patients, some patients appeared to be helped by the treatment. Weaknesses
in study design and reporting, however, made it unclear if benefits were caused by
the coenzyme Q10 or by something else.
Estimation Of Antioxidant Activity
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An end-point method for estimation of the total antioxidant activity in plant material
The 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical can be
generated by the enzymatic system formed by hydrogen peroxide and horseradish
peroxidase. This ABTS radical (ABTS+), a chromogen, is stable at room temperature
but is unstable above 35C and/or at pH values of above 7.5. Nevertheless, the mostimportant factor in its stability is the ABTS/ABTS+ concentration ratio in the medium.
The radical reacts with the antioxidant, L-ascorbic acid, with a high rate constant,
the stoichiometry of the reaction being 1 mol of L-ascorbic acid per 2 mol of
ABTS+reduced. Based on these considerations, a spectrophotometric end-point
method has been developed to evaluate L-ascorbic acid in aqueous media, and this
represents an improvement over the lag-method previously reported. Under optimal
conditions of temperature, pH and reagent concentration, the end-point method was
capable of determining L-ascorbic acid with a limit of quantification of 0.38 nmol. In
the assay described here, this ability is used to evaluate the total antioxidant activityof commercial citrus juices, in which ascorbic acid is a principal component.[32]
Estimation of the Antioxidant Activities of Flavonoids from Their Oxidation
Potentials
A simple electrochemical method for estimating the antioxidant activity (AA) of
flavonoids has been developed. The proposed method is based on a measurement of
the half-wave potential (E1/2) of the first oxidation wave of flavonoids by using flow-
through column electrolysis. At the same time, the lipid peroxidation (LPO) inhibiting
effects of these flavonoids were determined. A quantitative structure-activity
relationship was obtained to describe the AA of flavonoids: IC50(M) = 30.36 +151.50E1/2 (V) - 12.63log P (r = 0.852), where IC50 represents the concentration for
50% inhibition of LPO, and P represents the octanol/water partition coefficient. This
method is expected to be useful for the quick screening of flavonoid antioxidants, and
evaluating the AA of flavonoid-containing foods and medicinal plants.[32]
In Vitro Antioxidant Bioassays
DPPH Radical Scavenging Assay
The DPPH Radical Scavenging Effect Was Carried Out According To Method Used By
Blois (1958).4 Ml Of Each Sample (0.5mg/Ml)Was Added To 1.0 Ml DPPH MethanolSolution(0.000015 M) And Left Room Temperature For 10 Minutes. Absorbance Of The
Solution Was Measured At 520nm By Using A Spectrophotometer. Methanol(4 Ml) Plus
DPPH (1 Ml)Was Used As A Negative Control While The Ascorbic Acid (4 Ml , 5mcgml)
And DPPH ( 1 Ml) As A Positive Control.The Results Were calculated taking the mean
of triplicate values.[32]
Xanthine/Xanthine Oxidase Superoxide Scavenging System
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The reaction mixture is prepared by dissolving Sodium carbonate(0.53g),EDTA(0.004g)
and xanthine(0.05g) in 100 ml distilled water and then 10 ml NBT solution (0.025 mM)
is added.Inm 5 mcL of each sample(50 mg/ml),995 mcL of reaction mixture and 0.1
mcL of xanthine oxidase(0.1 mL) are added.the solution is mioxed and the absorbance
is taken at 560 nm.th reaction mixture (1000 mcL) and xanthine(0.1 mcL) are used asnegative control.superoxide dismutase (5 mcL),reaction mixture (995 mcL) and
xanthine oxidase are used as positive control.[32]
Antioxidant activity assay
Free radical scavenging capacity was measured using the radical chromogen 2,2-
diphenyl-1-picrylhydrazyl(Dpph)photometric assay.each sample stock solution
(1mg/mlMeOH)was diluted to final concenterations of 0.75,0.25,and 0.1mg/ml.a total
of 2.9ml of a 0.1Mm DPPH MeOH solution was added to 0.1ml of sample solution at
different concenterations and allowed to react at r.t.After 30mins ,the absorbance
values were spectrophotometrically measured at 517 nm to monitor thedisapperanceof the radical chromogen,and converted into the percentage antioxidant activity by
using the following equation:
%antioxidant activity=1-(Ab of sample/Ab of blank) x 100.
The positive controls were DPPH solution plus butylated hydroxyanisole(BHA),a
synthetic antioxidant compound,at the same concenterations as those of the
samples.[32]
Conclusion
An antioxidant is a molecule capable of slowing or preventing the oxidation of othermolecules. Oxidation is a chemical reaction that transfers electrons from a substance
to an oxidizing agent. Oxidation reactions can produce free radicals, which start chain
reactions that damage cells. Antioxidants terminate these chain reactions by
removing radical intermediates, and inhibit other oxidation reactions by being
oxidized themselves. The chief role of antioxidants in biology focused on their use in
preventing the oxidation of unsaturated fats, which is the cause of rancidity.
Antioxidants are almost used in all pharmaceutical products to prevent them from
degradation. Antioxidants are also widely used as ingredients in dietary supplements
in the hope of maintaining health and preventing diseases such as cancer andcoronary heart disease. The diet that is high in anti -oxidants neutralizes free radicals
.though there are lots of benefits of free radicals they can cause damage to healthy
cells as well. The diet that is high in anti-oxidants reduces free radicals there by
fighting ageing. Antioxidants have many industrial uses, such as preservatives in food
and cosmetics and preventing the degradation of rubber and gasoline.
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This review article is aimed to assist researchers conducting further research on
antioxidant activity of certain drugs. Till date there has been no marketed antioxidant
formulation and this project will serve as a base for anyone trying to come out with
such a formulation and thus simplify the use of antioxidants
References:-1. Matill HA (1947). Antioxidants. Annu Rev Biochem 16: 177192.
2. German J (1999). "Food processing and lipid oxidation". Adv Exp Med Biol 459: 23
50.
3. Jacob R (1996). "Three eras of vitamin C discovery". Subcell Biochem 25: 116..
4. Knight J (1998). "Free radicals: their history and current status in aging and
disease". Ann Clin Lab Sci 28 (6): 331-46.
5. Moreau and Dufraisse, (1922) Comptes Rendus des Sances et Mmoires de la
Socit de Biologie, 86, 321.
6.Wolf G (2005). "The discovery of the antioxidant function of vitamin E: the
contribution of Henry A. Mattill". J Nutr 135 (3): 363-6.
7.Sies H (1997). "Oxidative stress: oxidants and antioxidants". Exp Physiol 82 (2): 291-
5.
8. Vertuani S, Angusti A, Manfredini S (2004). "The antioxidants and pro-antioxidants
network: an overview". Curr Pharm Des 10 (14): 167794.
9.Valko M, Leibfritz D, Moncol J, Cronin M, Mazur M, Telser J (2007). "Free radicalsand antioxidants in normal physiological functions and human disease". Int J Biochem
Cell Biol 39 (1): 4484.
10.Valko M, Izakovic M, Mazur M, Rhodes C, Telser J (2004). "Role of oxygen radicals
in DNA damage and cancer incidence". Mol Cell Biochem 266 (12): 3756.
11.Finkel T, Holbrook NJ (2000). "Oxidants, oxidative stress and the biology of aging".
Nature 408 (6809): 239-47.
12.Sies H (1993). "Strategies of antioxidant defense". Eur J Biochem 215 (2): 213 9.
13.Imlay J (2003). "Pathways of oxidative damage". Annu Rev Microbiol 57: 395418.14.Turunen M, Olsson J, Dallner G (2004). "Metabolism and function of coenzyme Q".
Biochim Biophys Acta 1660 (1 2): 171 99.
15.Meister A, Anderson M (1983). "Glutathione". Annu Rev Biochem 52: 711 60.
16.Reiter RJ, Carneiro RC, Oh CS (1997). "Melatonin in relation to cellular
antioxidative defense mechanisms". Horm. Metab. Res. 29 (8): 363-72.
8/3/2019 An Overview of Antioxidants in Healthcare
20/22
17.Traber MG, Atkinson J (2007). "Vitamin E, antioxidant and nothing more". Free
Radic. Biol. Med. 43 (1): 415.
18.Sen C, Khanna S, Roy S (2006). "Tocotrienols:Vitamin E beyond tocopherols". Life
Sci 78 (18): 2088 98.
19.Bannister J, Bannister W, Rotilio G (1987). "Aspects of the structure, function, and
applications of superoxide dismutase". CRC Crit Rev Biochem 22 (2): 111-80.
20.Johnson F, Giulivi C (2005). "Superoxide dismutases and their impact upon human
health". Mol Aspects Med 26 (45):340-52.
21.Wood Z, Schrder E, Robin Harris J, Poole L (2003). "Structure, mechanism and
regulation of peroxiredoxins". Trends Biochem Sci 28 (1): 3240.
22.Nordberg J, Arner ES (2001). "Reactive oxygen species, antioxidants, and the
mammalian thioredoxin system". Free Radic Biol Med 31 (11): 1287-312.
23.Sohal R (2002). "Role of oxidative stress and protein oxidation in the aging
process". Free Radic Biol Med 33 (1): 3744.
24.Thomas D (2004). "Vitamins in health and aging". Clin Geriatr Med 20 (2): 259-74.
25.Shenkin A (2006). "The key role of micronutrients". Clin Nutr 25 (1): 113.
26.Dekkers J, van Doornen L, Kemper H (1996). "The role of antioxidant vitamins and
enzymes in the prevention of exercise-induced muscle damage". Sports Med 21 (3):
213-38.
27.Leeuwenburgh C, Heinecke J (2001). "Oxidative stress and antioxidants inexercise". Curr Med Chem 8 (7):829-38.
28.Hunt J (2003). "Bioavailability of iron, zinc, and other trace minerals from
vegetarian diets". Am J Clin Nutr 78 (3 Suppl): 633S-639S.
29.Coulter I, Hardy M, Morton S, Hilton L, Tu W, Valentine D, Shekelle P (2006).
"Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer".
Journal of general internal medicine: official journal of the Society for Research and
Education in Primary Care Internal Medicine 21 (7): 735-44.
30.Seifried H, McDonald S, Anderson D, Greenwald P, Milner J (2003)."The antioxidant
conundrum in cancer". Cancer Res 63 (15): 42958.
31.Prior R, Wu X, Schaich K (2005)."Standardized methods for the determination of
antioxidant capacity and phenolics in foods and dietary supplements". J Agric Food
Chem 53 (10):4290-302.
32.Cao G, Prior R (1998). "Comparison of different analytical methods for assessing
total antioxidant capacity of human serum". Clin Chem 44 (6 Pt 1): 130915.
8/3/2019 An Overview of Antioxidants in Healthcare
21/22
33.Dietz K, Jacob S, Oelze M, Laxa M, Tognetti V, de Miranda S, Baier M, Finkemeier I
(2006). "The function of peroxiredoxins in plant organelle redox metabolism". J Exp
Bot 57 (8):1697-709.
34.Creissen G, Broadbent P, Stevens R, Wellburn A,Mullineaux P (1996). "Manipulation
of glutathione metabolism in transgenic plants". Biochem Soc Trans 24 (2): 465-9.
35.Larsen P (1993). "Aging and resistance to oxidative damage in Caenorhabditis
elegans". Proc Natl Acad Sci U S A 90 (19): 89059.
About Authors:
Kushal H.Sanghvi
Third B. Pharm Student, MAEERS Maharashtra Institute of Pharmacy, Pune - 411038
E-mail [email protected]
Miss. Vaishali M. Sampat
Third B. Pharm Student, MAEERS Maharashtra Institute of Pharmacy, Pune - 411038
Mr.Sutar A.S.
Lecturer, MAEERS Maharashtra Institute of Pharmacy, Pune - 411038
http://www.pharmainfo.net/thinkofkushalhttp://www.pharmainfo.net/thinkofkushalmailto:[email protected]://www.pharmainfo.net/vaishalihttp://www.pharmainfo.net/vaishalimailto:[email protected]://www.pharmainfo.net/thinkofkushal8/3/2019 An Overview of Antioxidants in Healthcare
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Mr.Kannur D.M.
Senior Lecturer , MAEERS Maharashtra Institute of Pharmacy, Pune - 411038
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