OXIDATIVE STRESS AND BIOCHEMICAL CHANGES INDUCED BY ...

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44

Keshta et al. World Journal of Pharmacy and Pharmaceutical Sciences

OXIDATIVE STRESS AND BIOCHEMICAL CHANGES INDUCED BY

THIAMETHOXAM AND ACETAMIPRID INSECTICIDES IN RATS

Akaber T. Keshta1*, Ahmed A. Hataba

2, Hala M. I. Mead

3 and Nouran M. El-Shafey

3

1Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University,

Egypt.

2Organic Chemistry Division, Chemistry Department, Faculty of Science, Zagazig

University, Egypt.

3Pest Physiology Department, Plant Protection Research Institute, Agricultural Research

Center, Egypt.

ABSTRACT

Thiamethoxam (THIA) and Acetamiprid (AC) are neonicotinoid

insecticides used for pest control. They have potential toxicity to

mammals. The present study aimed to determine the oxidative stress of

THIA and AC in plasma and investigate the effect of them on heart,

brain and testis tissues in rats. Male albino rats weighing 90-110 g

were used. They were divided into 3 groups: negative control, THIA

and AC groups. THIA group was received THIA insecticide and AC

group was received AC insecticide at 1/10 LD50 of both insecticides by

oral administration. Our results demonstrated that THIA and AC

induced antioxidant, biochemical and histopathological alterations at

tested periods 10, 20 and 30 days. They significantly increased the

levels of malondialdehyde (MDA) and nitric oxide (NO), but they significantly decreased the

activities of catalase (CAT) and superoxide dismutase (SOD) at 10, 20 and 30 days

respectively (p<0.001). They significantly elevated the concentrations of total cholesterol and

triglycerides (TG). Also, these insecticides significantly increased the activities of lactate

dehydrogenase (LDH) and creatine kinase (CK-MB), whereas they significantly reduced

acetylcholinesterase (AChE) activity and testosterone level at the same periods respectively

(p<0.001). Moreover, THIA and AC prompted several changes in histopathological

examinations of heart, brain and testis compared to negative control group. This study

concluded that THIA and AC could stimulate oxidative toxicity, cardiotoxicity, neurotoxicity

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 6.041

Volume 5, Issue 6, 44-60 Research Article ISSN 2278 – 4357

*Corresponding Author

Dr. Akaber T. Keshta

Biochemistry Division,

Chemistry Department,

Faculty of Science,

Zagazig University,

Egypt.

Article Received on

14 March 2016,

Revised on 13 April 2016,

Accepted on 04 May 2016

DOI: 10.20959/wjpps20166-6837


45


and reproductive toxicity. Furthermore, the toxic effects of THIA may be more than AC on

plasma, heart, brain and testis. So, neonicotinoids should be used in agriculture applications

for a planned system.

KEYWORDS: Thiamethoxam, Acetamiprid, rats, oxidative stress, biochemical changes,

histopathological changes.

INTRODUCTION

Neonicotinoids are neuro-active insecticides. Their chemical structure is linked to nicotine.

They are the most used class of insecticides in the world. These insecticides are divided into

two types: N-nitroguanidines (imidacloprid, thiamethoxam, dinotefuran and clothianidin) and

N-cyanoaminides (acetamiprid and thiacloprid). They bind to nicotinic acetylcholine

receptors (nAChRs) and affect on the initiation of the electrical signal in the postsynaptic

neuron in sucking pests. The presence of an electron-withdrawing group, like cyano or nitro

group, is a vital structural of these insecticides and proposes to contribute to their selectivity.

These insecticides display selective toxicity for insects rather than for mammals. This

selectivity is responsible for reducing neonicotinoid mammalian toxicity.[1]

Thiamethoxam (THIA) has a systemic action for crop protection. It is highly effective for

whiteflies, thrips and pests of cotton and fruits. THIA metabolism has shown that its ‘magic

nitro group’ is transformed to produce nitrosoguanidine, aminoguanidine, guanidine and urea

derivatives. The mode of action can be depended on cell necrosis, apoptosis and an increase

in cell replication rate.[2]

Acetamiprid (AC) is very operative for aphids, leafhopper and pests of leafy vegetables. The

selectivity of AC is due to the electronegative nature of nitroguanidine, nitromethylene and

nitroamine which bind with an exact subsite in nAChRs. The metabolites could be considered

as an inhibitor of inducible nitric oxide synthase (iNOS).[3]

Certain neonicotinoids are connected to oxidative stress by the generation of free radicals.[4]

Furthermore, these insecticides may be prompted adverse effects on many organs such as

brain[5]

, testis[6]

and heart.[7]

Rats are considered deadly pests causing extensive food losses

and rapid distribution of many diseases.[8]

According to this study, THIA and AC may produce oxidative stress in plasma. They could

prompt several changes in the biochemical parameters and the histopathological studies in


46


heart, brain and testis tissues. Additionally, the bad effects of THIA may be more than AC on

plasma, heart, brain and testis in rats.

MATERIALS AND METHODS

Chemicals

Two used neonicotinoid insecticides: 1- Thiamethoxam insecticide (THIA) (PILOT 25%) is a

water soluble yellowish white crystalline powder. Its chemical name is: {3-[(2-chloro-5-

thiazolyl)methyl] tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine}. It was

purchased from ROTAM AGROCHEMICAL CO LTD-HONG KONG. 2- Acetamiprid

insecticide (AC) (MOSPILAN 20%) is a water soluble light blue fine powder without any

odor. Its chemical name is: ((E)-N1-[(6-chloro-3-pyridyl) methyl]-N2-cyano-N1-methyl

acetamidine). It was purchased from SUMITOMO CORPORATION SUMITOMO

CORPORATION under license of NIPPON SODA CO., LTD- TOKYO- JAPAN.

Determination of the median lethal dose (LD50) of AC

Acute toxicity study was determined according to the method of the Organization of

Economic Co-operation and Development guidelines by oral administration in male rats to

identify LD50 of AC.[9]

Animals and Experimental design

A total of 42 male Swiss adult albino rats weighing 90-110g were used in this study and

allowed one week for acclimatization prior to start of the experiment. They were housed in

the experimental animal house of the Faculty of Science, Zagazig University, Egypt. The

animals were maintained in the controlled environment of (temperature, humidity and light)

and fed on a commercial standard diet and tap water ad libitum.

The rats were divided into 3 groups as follows: 1- Negative control group: This group

comprised 6 rats. They were fed on normal diet and drunk normal water along period of the

experiment. 2- THIA group: This group comprised 18 rats. They were received THIA

insecticide orally at dose 156 mg/Kg body weight (1/10 oral LD50) dissolved in tap water

every day along 30 days.[10]

3- AC group: This group comprised 18 rats. They were received

AC insecticide orally at dose 100 mg/Kg body weight (1/10 oral LD50) dissolved in tap

water[11]

every day for 30 days.


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Sampling

The rats were scarified [2 rats from (negative control group) and 6 rats from (THIA and AC

groups) at 10, 20 and 30 days] after fasting 12 hours. Blood samples (serum and plasma)

were collected for antioxidant and biochemical studies at each period. Also, tissues (heart,

brain and testis) were collected for histopathological studies at each period.

Biochemical studies

Determination of MDA, NO, CAT and SOD assays

Plasma samples were prepared for malondialdehyde (MDA), nitric oxide (NO), catalase

(CAT) and superoxide Dismutase (SOD) assays according to the methods of Satoh[12]

,

Montgomery and Dymock[13]

, Aebi[14]

and Nishikimi et al.[15]

; respectively.

Determination of heart function tests

Serum samples were performed for heart function tests [lactate dehydrogenase (LDH) and

creatine kinase (CK-MB)] enzymes by using Bio-diagnostic kit methods according to the

methods of Pesce[16]

and Wu and Bowers[17]

; respectively.

Determination of total cholesterol and triglycerides

Serum samples were collected for total cholesterol and triglycerides (TG) tests by using Bio-

diagnostic kit methods according to the methods of Young[18]

and Stein[19]

; respectively.

Determination of AChE enzyme and testosterone ELISA

Acetylcholinesterase (AChE) and testosterone ELISA tests were estimated by using the

methods of Ellman et al.[20]

and Granoff and Abraham[21],

respectively in serum samples.

Histopathological examinations

Histopathological examinations were performed on the portion of the heart, brain and testis

tissues. The specimen were fixed in 10% formalin and embedded in paraffin wax. Heart,

brain and testis sections were cut at 5µm in thickness, stained with Hematoxylin and Eosin

(H&E.,) viewed light microscopy and examined histopathological changes according to

Lillie.[22]

Statistical analysis

The obtained data were evaluated by "SPSS" 14.0 for Microsoft Windows, SPSS Inc.[23]

The

values were expressed as mean±SD. The levels of markers were analyzed by one way


48


analysis of variance (ANOVA) and Dunnett's tests then followed by least significant

difference (LSD).

RESULTS

Acute toxicity study

The acute toxicity was estimated to determine LD50 of AC. Our results indicated that a dose

up to 500 mg/kg was considered to be safe, where no mortality was observed. The results

found that LD50 of AC= 1000 mg/kg body weight. Also, the oral LD50 value of THIA

was1563mg/kg that previously was measured. So, the used dose was 100 mg/kg body weight

of AC and 156 mg/kg body weight of THIA (1/10 LD50 of THIA and AC) in this study.

Biochemical studies

Determination of MDA, NO, CAT and SOD in plasma

THIA and AC significantly increased the levels of MDA and NO compared to negative

control group 18.73±1.36 (nmol/ml) and 26.51±2.34 (µmol/ml), but they significantly

reduced the activities of CAT and SOD compared to negative control group 238.15 ±10.63

(U/L) and 269.65±12.22 (U/L) after 10, 20 and 30 days; respectively, (p<0.001).The

alterations of THIA group were more than AC group, [Table 1].

Table: 1. Effects of THIA and AC on malondialdehyde (MDA), nitric Oxide (NO) levels,

catalase (CAT) and superoxide dismutase (SOD) activities at 10, 20, 30 days.

Groups Parameters Negative control 10 days 20 days 30 days

THIA

MDA (nmol/ml) 18.73±1.36 38.13±1.09 c

61.43±4.49 c 112.95±10.2 4

c

NO (µmol/ml) 26.51±2.34 66.17±3.80 c 92.50±3.53

c 163.57±7.41

c

CAT (U/L) 238.15±10.63 190.87±9.16 c

127.95±3.75 c 97.88±4.23

c

SOD (U/L) 269.65±12.22 185.12±10.09 c 100.91±4.89

c 51.90±4.35

c

AC

MDA (nmol/ml) 18.73±1.36 41.18±3.02 c

72.31±5.61 c 93.67±4.11

c

NO (µmol/ml) 26.51±2.34 52.47±2.91 c

83.32±4.90 c 122.15±8.11

c

CAT (U/L) 238.15 ± 10.63 208.55 ± 6.94c

165.51 ± 10.72 c 101.38 ±2.33

c

SOD (U/L) 269.65±12.22 191.70±9.74 c 98.73±2.26

c 78.52±4.97

c

Data are expressed as mean±SD of rats for each group. P: Significant difference when

compared to negative control group. (N.S) Non-significant: (P>0.05); (a) Significant (P <

0.05); (b) highly significant (P < 0.01); (c) very highly significant: (P < 0.001).

Heart function tests

THIA and AC significantly elevated the activities of LDH and CK-MB enzymes compared to

negative control group 251.10±11.36 (U/L) and 101.73±6.79 (U/L) after 10, 20 and 30 days;

respectively, (p<0.001). The elevations of THIA group were more than AC group, [Table 2].


49


Table 2. Effects of THIA and AC on lactate dehydrogenase (LDH) and creatine kinase

(CK-MB) activities at 10, 20, 30 days.


THIA LDH (U/L) 251.10±11.36 2611.00±248.19c 3217.17±88.13

c 4570.00±305.32

c

CK-MB (U/L) 101.73±6.79 219.57±4.65c 251.33± 20.57

c 467.4±23.36

c

AC LDH (U/L) 251.10 ±11.36 1719.50 ±117.53c 1945.83±34.40

c 2 886.00±52.51

c

CK-MB (U/L) 101.73±6.79 126.27±6.52b 158.83±4.58

c 201.80±10.39

c




TG and total cholesterol

The concentrations of TG and total cholesterol were revealed a gradually significant increase

in treated groups compared to negative control group 62.38±4.29 (mg/dl) and 83.80±4.56

(mg/dl) after 10, 20 and 30 days; respectively, (p<0.001). The changes of THIA group were

more than AC group, [Table 3].

Table: 3 Effects of THIA and AC on triglycerides (TG) and total cholesterol

concentrations at 10, 20, 30 days.

Groups Parameters Negative

control 10 days 20 days 30 days

THIA TG (mg/dl) 62.38± 4.29 74.95±1.90

c 86.01±3.72

c 112.83 ±8.03

c

Total cholesterol (mg/dl) 83.80± 4.56 115.47±4.59c

137.31±4.48c

162.21±3.89c

AC TG (mg/dl) 62.38± 4.29 71.25±0.70

c 81.48 ± 1.30

c 86.75±1.78

c

Total cholesterol (mg/dl) 83.80± 4.56 95.62± 2.85c

112.78 ± 4.68c

150.87±5.72c




AChE activity and Testosterone hormone

AChE activity and Testosterone level were shown a gradually significant reduction in treated

groups compared to negative control group 378.77 ±43.45 (U/L) and 3.48 ±0.39 (ng/ml) after

10, 20 and 30 days; respectively, (p<0.001). The reductions of THIA group were more than

AC group, [Table 4].


50


Table: 4. Effects of THIA and AC on acetylcholinesterase (AChE) activity and

testosterone level at 10, 20, 30 days.


THIA AChE (U/L) 378.77±43.45 270.71±17.26

c 227.80±5.71

c 154.28±5.02

c

Testosterone (ng/ml) 3.48±0.39 1.48±0.30 c 0.44±0.09

c 0.14 ±0.80

c

AC AChE (U/L) 378.77±43.45 246.10±7.62

c 221.12±6.85

c 199.03±6.66

c

Testosterone (ng/ml) 3.48±0.39 2.48±0.23 c 1.55±0.24

c 0.85±0.11

c




Histopathological examinations

The histopathological studies in different organs (heart, brain and testis) were illustrated at

figures [1 (A to G), 2 (A to G) and 3(A to G)] respectively at 10, 20 and 30 days.

The histopathological studies in different organs were approved by the biochemical analyses

at 10, 20 and 30 days in both treatments. There was a relation between the increase in extent

of the damages in different organs and the increase in periods of treatments of these

insecticides. The changes occurred in THIA group may be more than the changes occurred in

AC group in different tissues.


51


Fig.1: Photomicrograph of histopathological examination in heart tissues in studied

groups. 1A): Negative control group showing normal structure: bundles of cardiac

muscles (B), stroma (S) and red blood cells (R) (H&E., X100). In THIA group, 1B):

after10 days showing small sized atrophic muscles (A). 1C): after 20 days showing

atrophic muscles (A) and area of hemorrhage (H). 1D): after 30 days showing large

areas of hemorrhage (H) and necrosis (N). In AC group, 1E): after 10 days showing

normal cardiac muscles (CM). 1F): after 20 days showing area of hemorrhage (H) and

atrophic muscles (A). 1G): after 30 days showing area of hemorrhage (H), atrophic

muscles (A) and small area of necrosis (N) (H&E., X200).


52


Fig 2: Photomicrograph of histopathological examination in brain tissues (cerebrum

part) in studied groups. 2A): Negative control group showing neuronal cells (NC) and

neurofibrillary eosinophilic material (NE). In THIA group, 2B): after 10 days showing

separations of the brain tissue by areas of edema (E). 2C): after 20 days showing areas

of edema (E) and atrophic neurons (A). 2D): after 30 days showing large areas of edema

(E) and necrosis (N). In AC group, 2E): after 10 days showing mild areas of edema (E).

2F): after 20 days showing areas of atrophic neurons (A) and gliosis (G). 2G): after 30

days showing atrophic neurons (A) and large areas of edema (E). (H&E., X200).


53


Fig.3: Photomicrograph of histopathological examination in testis tissues in studied

groups. 3A): negative control group showing seminiferous tubules lined by

spermatogenic layers: primary spermatocytes (P), secondary spermatocytes (SE),

sperms (S) and basement membrane (B) (H&E.,X 400). In THIA group, 3B): after 10

days showing mild normal seminiferous tubules. 3C): after 20 days showing sloughing

of spermatogenic cells (S) and reduced number of sperms (R). 3D): after 30 days

showing reduced number of spermatogenic layers (R), edema (E), disappear sperms in

some regions (D) and congestion (C). In AC group, 3E): after 10 days showing mild

normal seminiferous tubules. 3F): after 20 days showing areas of edema (E) and

reduced number of sperms (R). 3G): after 30 days showing sloughing of spermatogenic

cells (S), areas of edema (E), reduced number of sperms (R) and congestion (C) (H&E.,

X 200).


54


DISCUSSION

Neonicotinoids undergo trans-epithelial absorption across intestinal cells resulting in their

toxicity when they accumulate within the body organs. They can be induced oxidative stress

by producing reactive oxygen species (ROS). The measurement of oxidative stress

biomarkers may be very important to study oxidative damage caused destruction of various

tissues.[24]

THIA, AC and their metabolites may be regarded as an agonist of nicotine (main

constituent of neonicotinoid) and iNOS. THIA and AC metabolized to 6-chloramphenicol

acid forming carbamidine inhibited iNOS.[25]

This study reported that THIA and AC caused a

significant increase in the levels of MDA, NO and a significant decrease in the activities of

CAT, SOD in plasma after 10, 20 and 30 days respectively (p<0.001) compared to negative

control group (Table1). Elevated nitric oxide (NO) and MDA levels might be caused tissue

damage by lipid peroxidation (LP) induction leading to disorganization of the membrane.

MDA is an important indicator of oxidative stress in cells.[26]

THIA and AC metabolites

produce superoxide anion and hydrogen peroxide induced depletion the antioxidants.

Moreover, nicotine may stimulate LP and NO production and drop in CAT and SOD

activities. SOD is responsible for catalyzing the conversion of the superoxide ion into water

and molecular oxygen. Also, CAT is an essential defense enzyme against oxygen species.[27]

Our results were agreement with many authors, Kapoor et al.[28]

who explained that

imidacloprid (IMI) reduced in SOD and CAT activities, but it increased MDA level in ovary

due to oxidative stress and caused the imbalance of hormones. Duzguner and Erdogan[29]

who

reported that IMI elevated NO production due to iNOS induction in liver and plasma. Also,

IMI raised MDA and LP levels because IMI acted on unsaturated fatty acids of phospholipid

components of membranes and produced tissue damage. EL-Gendy et al. [30]

who disagreed

with our results as IMI caused the elevations in CAT and SOD activities in liver attributed to

defense mechanisms against oxidative damage.

Heart could be pumped blood that provided the body with oxygen and removed metabolic

wastes. CK-MB and LDH are indicators to loss enzymes from the injured heart tissue to

blood when its membrane becomes rupture and they are the useful markers of myocardial

infarction.[31]

Both insecticides significantly elevated in the activities of LDH and CK-MB. Also, it caused

a significant increase in the concentrations of TG and total cholesterol after different periods

respectively (p<0.001) compared to negative control group (Table2, 3). The biochemical


55


changes in secreted heart enzymes and synthetic capacity of cardiac cells can be confirmed

by histopathological analysis. THIA and AC induced atrophic cardiac muscles, hemorrhage

and necrosis in cardiac muscles (Fig.1 [A to G]). The elevations of total cholesterol and TG

are due to the accumulation of lipids in heart causing hyperlipidemia and irreversible damage

in it. Also, the rises of LDH and CK-MB enzymes reflect on the alterations permeability

fluids in cardiac muscle and cause edema. LDH, cholesterol and triglycerides may be linked

to cardiovascular risk factors. However, THIA and AC metabolites could generate ROS and

damage the myocardium tissues. Nicotine could release catecholamines and stimulate

lipolysis. It may induce cardiac edema and necrosis due to oxidative stress.[32]

Our results were in harmony, Park et al.[33]

who discussed that IMI increased LDH activity

and caused cardiac necrosis. Gokulakrisnan et al.[34]

who demonstrated that cigarette smoking

(contain nicotine) induced cardiac damage by the elevation in CK-MB activity due to LP and

protein oxidation. Goyal et al.[35]

who showed thiacloprid produced mild myocardial

hemorrhages and congestion due to metabolite toxicities, oxidative stress and endocrine

disorders. Shalaby et al.[36]

who described that THIA caused a rise in TG concentration after

5 and 10 days due to a shift in lipid metabolism.

Brain plays a critical role in the body’s sensitivity and response to stress. It is susceptible to

oxidative damage due to LP that damaged neural cells. Acetylcholinesterase (AChE) is a key

enzyme in detecting the neurotoxicity.[37]

The current results observed a significant reduction in AChE activity after different studied

periods respectively (p<0.001) compared to negative control group (Table 4). The

biochemical alteration in secreted brain enzyme and synthetic capacity of brain cells can be

confirmed by histopathological study. THIA and AC groups produced areas of edema,

atrophic neurons, area of necrosis in neural cells and gliosis after 10, 20 and 30 days (Fig.2

[A to G]). Neonicotinoids act on the central nAChRs and cause changes of the

phosphorylation state of AChE, nAChRs and choline action producing an imbalance in the

cholinergic neurotransmission. Also, the decline in AChE activity could be caused gliosis.

Nicotine could induce brain edema and brain inflammation.[38]

On a hand, our records were in

the same line with Rodrigues et al.[39]

who suggested that THIA dropped AChE activity after

1 week due to affecting on AChE or nAChRs.


56


Testosterone hormone plays a key role in the growth of male reproductive tissues and

stimulates spermatogenesis in testis.[40]

THIA and AC caused a significant decrease in the

testosterone level compared to negative control group (p<0.001) respectively at tested periods

(Table4). This result approved by histological examination in testicular tissue and impaired of

its function of spermatogenesis. They induced sloughing of spermatogenic cells, reduced

number of sperms and spermatogenic layers in seminiferous tubules and loss sperms in some

regions (Fig.3 [A to G]). THIA, AC and their metabolites induced oxidative stress leading to

loss testicular and spermatogonia tissues.[41]

Nicotine may cause a decreasing in sperm

function. Also, nAchRs could be acted on these insecticides and suppressed gonadotropins

releasing that caused the hormonal imbalance of luteinizing hormone (LH) and follicle-

stimulating hormone (FSH) due to the fall in sperm production.[42]

Our study agreed with

Soujanya et al.[43]

who found that IMI prompted degeneration seminiferous tubules due to

oxidative stress and triggered a reduction in the testosterone level.

Nitro group is higher reactivity and stronger in electrophilicity than cyano group because it

reduced the stability of the benzene ring as result of its resonance structure: O=N+-O

-- and O

--

- N+=O. It may be resistant to oxidative degradation prompted mutagenicity. The lower

toxicity of AC can be attributed to its rapid metabolism and less bioaccumulative, while the

higher toxicity of THIA can be known as more bioaccumulative.[44]

According to these

results, the biochemical alterations were confirmed by histopathological alterations in

different organs at 10, 20 and 30 days.

CONCLUSION

According to our data, we found that THIA and AC may induce antioxidant alterations in

plasma. They could be neurotoxic, cardiotoxic and testicular toxic. The adverse effects of

THIA may be more than AC on plasma, heart, brain and testis. Use of these insecticides

should be under control to damage the pests with avoiding possible bad effects on the

environment.

ACKNOWLEDGEMENT

Authors are very much thankful to Chemistry department, Science Faculty, Zagazig

University, Egypt for providing the place of study.


57


REFERENCES

1. Jeschke P, Nauen R. Neonicotinoids from zero to hero in insecticide chemistry. J Pest

Manag Sci, 2008; 64: 1084–1098.

2. Green T, Toghill A, Lee R, Waechter F, Weber E, Noakes J. Thiamethoxam induced

mouse liver tumors and their relevance to humans. Part 1: mode of action studies in the

mouse. J Toxicol Sci, 2005; 86: 36- 47.

3. Ford KA, Casida JE. Unique and common metabolites of thiamethoxam, clothianidin and

dinotefuran in mice. J Chem Res Toxicol, 2006; 19: 1549-1555.

4. Hoshi N, Hirano T, Omotehara T, Tokumoto J, Umemura Y, Mantani Y, Tanida

T, Warita K, Tabuchi Y, Yokoyama T, Kitagawa H. Insight into the mechanism of

reproductive dysfunction caused by neonicotinoid pesticides. J Biol Pharm Bull, 2014;

37: 1439-1443.

5. Kimura-Kuroda J, Komuta Y, Kuroda Y, Hayashi M, Kawano H. Nicotine-like effects of

the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from

neonatal rats. J PloS One, 2012; 7: e32432-e32443.

6. Bal R, Naziroğlu M, Türk G, Ökkes Y, Kuloğlu T, Etem E, Baydas G. Insecticide

imidacloprid induces morphological and DNA damage through oxidative toxicity on the

reproductive organs of developing male rats. J Cell Biochem Funct, 2012; 30: 492-499.

7. Lin PC, Lin HJ, Liao YY, Guo HR, Chen KT. Acute poisoning

with neonicotinoid insecticides: a case report and literature review. J Basic Clin

Pharmacol Toxicol, 2013; 112: 282-286.

8. Meerburg BG, Singleton GR, Leirs H. The Year of the Rat ends: time to fight hunger. J

Pest Manag Sci., 2009; 65: 351–352.

9. OECD (Organisation for Economic Co-operation and Development). Guideline for

Testing of Chemicals. No.420: Acute Oral Toxicity-Fixed Dose Method. Organisation for

Economic Cooperation and Development, Paris, 1992.

10. Maienfisch P, Brandl F, Kobel W, Rindlisbacher A, Senn R. CGA 293343: a novel,

broad-spectrum neonicotinoid insecticide. (In: Yamamoto, I., Casida, J.E. (eds.),

Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Springer, Verlag.

Tokyo, 1999; 177–209.

11. Tang H, Li J, Hu H, Xu P. A newly isolated strain of Stenotrophomonas sp. hydrolyzes

acetamiprid, a synthetic insecticide. J Process Biochem, 2012; 47: 1820-1825.

12. Satoh K. Serum Lipid Peroxide in cerebrovascular disorders determined by a new

colorimetric method. J Clin Chim Acta, 1978; 90: 37-43.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Green%20T%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed/?term=Toghill%20A%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed/?term=Lee%20R%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed/?term=Waechter%20F%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed/?term=Weber%20E%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed/?term=Noakes%20J%5BAuthor%5D&cauthor=true&cauthor_uid=15716477

http://www.ncbi.nlm.nih.gov/pubmed?term=Hirano%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Omotehara%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Tokumoto%20J%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Umemura%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Mantani%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Tanida%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Tanida%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Warita%20K%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Tabuchi%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Yokoyama%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Kitagawa%20H%5BAuthor%5D&cauthor=true&cauthor_uid=25177026

http://www.ncbi.nlm.nih.gov/pubmed?term=Lin%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=23078648

http://www.ncbi.nlm.nih.gov/pubmed?term=Liao%20YY%5BAuthor%5D&cauthor=true&cauthor_uid=23078648

http://www.ncbi.nlm.nih.gov/pubmed?term=Guo%20HR%5BAuthor%5D&cauthor=true&cauthor_uid=23078648

http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20KT%5BAuthor%5D&cauthor=true&cauthor_uid=23078648

http://www3.interscience.wiley.com/journal/121686000/abstract


58


13. Montgomery HC, Dymock JF. The determination of nitrite in water. J Analyst, 1961; 86:

414- 416.

14. Aebi H. Catalase in vitro. J Method Enzymol, 1984; 6: 105-121.

15. Nishikimi M, Appaji N, Yogi K. The occurrence of superoxide anion in the reaction of

reduced phenazine methosulfate and molecular oxygen. J Biochem Biophys Res

Commun, 1972; 46: 849– 854.

16. Pesce A. Lactate dehydrogenase, Kaplan et al A Clin. Chem. the C.V. Mosby Co. St.

Louis. Toronto. Princeton, 1984; 1124-1127.

17. Wu AHB, Bowers CNJ. Evaluation and comparison of immunoinhibition and

immunoprecipitation methods for differentiating MB from BB and macro forms of

creatine kinase isoenzymes in patients and healthy individuals. J Clin Chim, 1982; 2017.

18. Young DS. Effects of disease on Clinical Lab. Tests, 4th ed. AACC, 2001.

19. Stein EA. Lipids, lipoproteins, and apolipoproteins. In: Tietz NW, (ed.). Fundamentals of

Clinical Chemistry. 3rd ed. Philadelphia: WB Saunders, 1987; 448-481.

20. Ellman GL, Courtney DK, Andreas V, Featherstone RM. A new and rapid colorimetric

determination of acetylcholinesterase activity. J Biochem Pharmacol, 1961; 7: 88–95.

21. Granoff AB, Abraham GE. Peripheral and adrenal venous levels of steroids in a patient

with virilizing adrenal adenoma. J Obstet Gynecol, 1979; 53: 111-115.

22. Lillie RD. Histopathologic technique. Practical histochemistry, 1976; 95: 851-859.

23. Levesque RSPSS. Programming and Data Management: A Guide for SPSS and SAS

Users, (4th ed), SPSS Inc., ChicagoIll, 2007.

24. Zama D, Meraihi Z, Tebibel S, Benayssa W, Benayache F, Benayache S, Vlitinck AJ.

Chlorpyrifos- induced oxidative stress and tissue damage in the liver, kidney, brain and

fetus in pregnant rats: the protective role of the butanolic extract of Paronychie argentea

L. Indian J Pharm., 2007; 39: 145–150.

25. Tomizawa M, Casida JE. Neonicotinoid insecticide toxicology: mechanism of selective

action. J Annu Rev Pharmacol Toxicol, 2005; 45: 247-268.

26. Mansour SA, Mossa AH. Oxidative damage, biochemical and histopathological

alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. J Pestic

Biochem Phys., 2010; 96: 14–23.

27. Chelikani P, Fita I, Loewen PC. Diversity of structures and properties among catalases. J

Cell Mol Life Sci., 2004; 61: 192–208.

http://www.ncbi.nlm.nih.gov/pubmed?term=Aebi%20H%5BAuthor%5D&cauthor=true&cauthor_uid=6727660


59


28. Kapoor U, Srivastava MK, Bhardwaj S, Srivastava LP. Effect of imidacloprid on

antioxidant enzymes and lipid peroxidation in female rats to derive its No Observed Effet

Level (NOEL). J Toxicol Sci., 2011; 35: 577-581.

29. Duzguner S, Erdogan S. Acute oxidant and inflammatory effects of imidacloprid on the

mammalian central nervous system and liver in rats. J Pestic Biochem Phys, 2010; 97:

13–18.

30. El-Gendy KS, Aly NM, Mahmoud FH, Kenawy A, El-Sebae AKH. The role of vitamin

C as antioxidant in protection of oxidative stress induced by imidacloprid. J Food Chem

Toxicol, 2010; 48: 215–221.

31. Antman E. Elevation Myocardial Infarction: Pathology, Pathophysiology and Clinical

Features. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Ed. Peter

Libby, Robert O. Bonow, Douglas L. Mann, Douglas P. Zipes. Philadelphia: Saunders,

Chapter 51: 2007.

32. Balakrishnan A, Menon V. Protective effect of hesperidin on nicotine induced toxicity in

rats. Indian J Exp Biol, 2007; 45: 194-202.

33. Park Y, Kim Y, Kim J, Yoon KS, Clark J, Lee J, Park Y. Imidacloprid, a neonicotinoid

insecticide, potentiates adipogenesis in 3T3-L1adipocytes. J Agric Food Chem, 2013; 9:

255-259.

34. Gokulakrisnan A, Jayachandran DB, Thirunavukkarasu C. Attenuation of the cardiac

inflammatory changes and lipid anomalies by (−)-epigallocatechin- gallate in cigarette

smoke-exposed rats. J Mol Cell Biochem, 2011; 354: 1-10.

35. Goyal S, Sandhu HS, Sandhu RS. Histopathological alterations induced after oral sub-

acute thiacloprid toxicity in Gallus domesticus. J Vet Arhiv, 2010; 80: 673-682.

36. Shalaby SEM, Farrag ARH, El-Saed GSM. Toxicological potential of thiamethoxam

insecticide on albino rats and its residues in some organs. JAMSR, 2010; 5: 165-172.

37. Ljubisavljevic S, Stojanovic I, Pavlovic R, Sokolovic D, Pavlovic D, Cvetkovic T,

Stevanovic I. Modulation of nitric oxide synthase by arginase and methylated arginines

during the acute phase of experimental multiple sclerosis. J Neurol Sci., 2012; 318: 106 -

111.

38. Silver J, Miller JH. Regeneration beyond the glial scar. J Nature Rev Neurosci, 2004; 5:

146-156.

39. Rodrigues KJA, Santana MB, Do N, JLM P ̧ o-Diniz DLW, Maués LAL, Santos SN,

Ferreira VMM, Alfonso M, Durn R, Faro LRF. Behavioral and biochemical effects of

http://link.springer.com/search?facet-author=%22A.+Gokulakrisnan%22

http://link.springer.com/search?facet-author=%22C.+Thirunavukkarasu%22


60


neonicotinoid thiamethoxam on the cholinergic system in rats. J Ecotox Environ Safe,

2010; 73: 101–107.

40. Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement

therapy: a review. J Ther Clin Risk Manag, 2009; 5: 427–448.

41. Jiao-jiao Z, Yi W, Hai-yang X, Meng-xue L, Wen-hao L, Kai-ge M, Xian-zhong W, Jia-

hu Z. Oxidative Stress: role in acetamiprid-induced impairment of the male mice

reproductive system. J Agric Sci in China, 2011; 10: 786-796.

42. Ngoula F, Watcho P, Dongmo MC, Dongmo MC, Kenfack A, Kamtchouing P,

Tchoumboue J. Effects of pirimiphos-methyl (an organophosohate insecticide) on the

fertility of adult male rats. Afr J Health Sci., 2007; 7: 3-9.

43. Soujanya S, Lakshman M, Gopala RA. Protective role of vitamin c against the

histopathological and ultrastructural changes induced by imidacloprid in testis of male

rats. Int J Life Sci Biotechnol Pharma Res, 2013; 2: 92-97.

44. Guillen J, Bielza P. Thiamethoxam acts as a target-site synergist of spinosad in resistant

strains of frankliniella occidentalis. J Pest Manag Sci, 2013; 69: 188–194.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701485

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701485

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