Benchmark Dose Approach to DNA and Liver Damage by Chlorpyrifos and Imidacloprid in Male Rats: The Protective Effect of a Clove-Oil-Based Nanoemulsion Loaded with Pomegranate Peel Extract.

Pesticides are widely used around the world to increase crop production. They also have negative impacts on animals, humans, and the ecosystem. This is the first report evaluating a novel pomegranate-extract-loaded clove-oil-based nanoemulsion (PELCN) and its potential for reducing oxidative stress and DNA damage, as well as its hepatoprotective effects against imidacloprid (IM) and chlorpyrifos (CPF) toxicity in male rats. The benchmark dose (BMD) approach was also used to study the dose-response toxicity of IM and CPF. IM and CPF were administered daily for 28 days at doses of 14, 28, and 54 mg/kg body weight (bw) of IM and 1, 2, and 4 mg/kg bw of CPF via drinking water. The PELCN was administered orally at a dose of 50 mg/kg bw/day of pomegranate extract, 500 mg/kg bw of the clove oil nanoemulsion, and IM or CPF at high doses in the drinking water. In male rats, IM and CPF caused a reduction in body weight gain and hepatotoxic effects as evidenced by increases in the liver enzymes AST, ALT, and ALP. They caused oxidative damage in the liver of male rats as indicated by the decreased liver activity of the GST, GPX, SOD, and CAT enzymes and decreased serum TAC. IM and CPF produced a significant dose-dependent increase in DNA damage in hepatocyte cells, resulting in moderate to severe liver damage with cells that are more inflammatory and have enlarged sinusoids and compacted nuclei. IM had a higher BMD than CPF for both body and liver weight, suggesting that CPF was more dose-dependently toxic than IM. Albumin was a highly sensitive liver biomarker for IM, while total protein was a biomarker for the CPF-treated rats. GPx was an extremely sensitive biomarker of oxidative stress in the IM treatment, while CAT and GPx were highly sensitive parameters in the CPF-treated rats. Therefore, at comparable doses, CPF has a higher potential to cause liver damage and oxidative stress than IM. The hepatotoxicity of IM and CPF can be mitigated by administering a nanoemulsion containing clove oil and pomegranate extract. The nanoemulsion acts as a protector against the oxidative stress caused by these insecticides, especially at high doses. The nanoemulsion based on clove oil increases the bioavailability and stability of the pomegranate extract, which has antioxidant properties.

Benchmark dose and the adverse effects of exposure to pendimethalin at low dose in female rats.

Pendimethalin (PND) is a dinitroaniline herbicide widely used to control broadleaf and annual grasses. Although the acute oral toxicity of PND is >5 g/kg b.wt. in humans (LD50 for rats >5000 g/kg b.wt.), it has been classified as a possible human carcinogen. It is still used in agriculture so agricultural workers and their families, as well as consumers, can be exposed to this herbicide. The present study is the first report investigating the dose-response effect using the benchmark dose (BMD) and the adverse effects of exposure to PND at low dose via apoptosis responses linked to the expression of tumour necrosis factor-α (TNF-α), FAS and BAX proteins; oxidative stress; and DNA and liver damage in female rats. The rats were exposed to PND via drinking water at doses equivalent to no-observed-adverse-effect level (NOAEL = 100 mg/kg b.wt.), 200 and 400 mg/kg b.wt. for 28 days. PND caused the overexpression of TNF-α, FAS and BAX; increased the levels of serum liver biomarkers; and increased oxidative stress in the liver and erythrocytes. Furthermore, it induced DNA and liver damage in a dose-dependent manner. The BMD showed that serum alkaline phosphatase (ALP) and total antioxidant capacity (78.4 and 30.1 mg/kg b.wt./day, respectively), lipid peroxidation in liver tissue (30.9 mg/kg b.wt./day), catalase in erythrocytes (14.0 mg/kg b.wt./day) and FAS expression in liver tissue (6.89 mg/kg b.wt./day) were highly sensitive biomarkers of PND toxicity. Our findings suggest the generation of reactive oxygen species as a possible mechanism of PND-induced gene overexpression of tumour necrosis factor-α (TNF-α), FAS and BAX proteins, oxidative stress and DNA and liver damage in female rats.

Detoxification gene expression, genotoxicity, and hepatorenal damage induced by subacute exposure to the new pyrethroid, imiprothrin, in rats.

The pyrethroid imiprothrin is widely used worldwide for control of insects in the agriculture and public health sectors. No sufficient information is however available concerning detoxification gene expression, i.e., cytochrome P450 1A2 (CYP1A2) and metallothionein 1a gene, oxidative stress, lipid peroxidation, DNA damage, cytotoxicity, genotoxicity, and organ injury induced by imiprothrin in mammals. This study is designed to explain the mechanism of imiprothrin induced detoxification gene expression, DNA damage, cytotoxicity, genotoxicity, and organ toxicity in male rats. The benchmark dose (BMD) was calculated to find the best sensitive markers to imiprothrin toxicity. Imiprothrin was injected intraperitoneally (i.p.) into male rats once a day for 5 days with doses of 19, 38, and 75 mg/kg body weight (b.wt.). Imiprothrin caused a significant increase in lipid peroxidation and changes in oxidative stress biomarkers in treated rats. Significant dose-dependent changes in the liver and kidney biomarkers were observed. Histopathological alterations were seen in the liver and kidney tissue of male rats. Imiprothrin also significantly increased chromosomal aberrations (CA) and micronuclei in bone-marrow cells, and induced lipid peroxidation, oxidative stress, cytotoxicity, and liver and kidney dysfunction, and damage. Imiprothrin induced DNA damage and over detoxification gene expression of CYP1A2 and metallothionein 1a gene in hepatocytes of male rats. Imiprothrin thus shows clastogenic and genotoxic potential. The mechanism for hepatorenal toxicity and injury, genotoxicity/cytotoxicity of imiprothrin might be due to enhanced lipid peroxidation, and oxidative stress associated with overproduction of free radicals, especially reactive oxygen species, and an imbalance in redox status. From the BMD models, aspartate aminotransferase (AST), total protein, uric acid, superoxide dismutase (SOD), and micronuclei (MPEs) were very sensitive markers to imiprothrin toxicity.

Over-gene expression in the apoptotic, oxidative damage and liver injure in female rats exposed to butralin.

The present study is the first report for studying the toxic effects of butralin herbicide on COX2, BAX, and Bcl2 gene expression, oxidative stress, and liver damage in female rats. Female rats were received butralin in drinking water for 28 days at concentration 4.16, 312, and 3120 mg/L that corresponded to the acceptable daily intake (ADI), no observed adverse effect level (NOAEL), and 10 NOAEL, respectively. Butralin decreased body weights and increased relative liver weight of female rats exposed to high dose. It caused significant elevation in liver function enzymes, lipid peroxidation, and reactive oxygen species (ROS). Antioxidant enzymes were decreased in liver tissue by increasing the dose. Butralin induced over-expression in the apoptotic related genes including COX2, BAX, and Bcl2 and pathological alteration in the liver of female rats especially at a high dose. It can be concluded that butralin induced oxidative damage and liver injure. The mechanism of damage could be due to generate reactive oxygen species, and increase lipid peroxidation that causes over-expression in the apoptotic related genes including COX2, BAX, and Bcl2. From the Benchmark dose (BMD) approach, there is dose-dependent manner in body weight, AST, ALT, and ALP, and ALT is a very sensitive parameter.

In utero exposure to organochlorine pesticide residues and their potential impact on birth outcomes and fetal gender.

Being the largest agriculture country in the Arab world, Egypt was one of the major consumer of organochlorine pesticides (OCPs) in this area, continued to have a heavy burden of OCPs in the environment. There is growing concern that OCPs could pass from the maternal circulation through the placenta to the fetal circulation and pose several health risks to their fetuses. The current study was intended to identify OCPs residue exposure in healthy pregnant women and to justify the potential impacts of these residues on their fetuses. In this study, the prevalence of 18 OCPs was estimated in 81 maternal and cord blood samples, using Agilent 7890, gas chromatograph equipped with micro-electron capture detector (GC-µECD). Our data signposted that the heptachlor epoxide has the highest detection rate among all residues in both maternal (32%) and cord blood serum (27.16%). DDTs were still quantifiable, but with the lowest quantifiable percentage. More than 85% of mothers' serum with detectable residues transfer OCPs residue to their fetuses in a statistically significant manner (x = 42.9, p value < 0.001). The present findings showed no significant growth retardation, or preterm delivery induced by in utero exposure to the most abundant residues. There is growing evidence that exposure to OCPs residue has profound impact on sex ratio. Methoxychlor, in this study be deemed as testosterone triggers which yields high boys ratio (x = 4.37, p < 0.05). In conclusion, Egypt continued to have a heavy burden of OCPs residues, and fetuses and infants are especially the most vulnerable groups to their adverse health effects. Exposure to OCPs may disrupt the maternal hormones, which regulate the offspring gender, but these results need to be validated in larger sample sizes.

Novel Synthesis and Biological Evaluation of the First Pyrazole Thioglycosides as Pyrazofurin Analogues.

This study reports a novel and efficient method for the synthesis of the first reported novel class of pyrazole thioglycosides 6a-h. These series of compounds were designed through the reaction of sodium 2-cyano-3-oxo-3-(4-substitutedphenylamino)prop-1-ene-1,1-bis(thiolate) salts 2 with hydrazine hydrate in ethanol at room temperature to give the corresponding sodium 5-amino-4-(substitutedphenylcarbamoyl)-1H-pyrazole-3-thiolates 3a-d. The latter compounds were treated with protected α-D-gluco- and galacto-pyranosyl bromides 4a,b in DMF at ambient temperature to give in a high yields the corresponding pyrazole thioglycosides 6a-h. Treatment of pyrazole salts 3a-d with hydrochloric acid at amobient temperature afforded the corresponding 3-mercaptopyrazole derivatives 5. The latter compounds were treated with peracetylated sugars 4 in sodium hydride in ethanol at ambient temperature to tolerate the S-glycosyl 6a-h compounds. Ammonolysis of the pyrazole thioglycosides 6a-h afforded the corresponding free thioglycosides 7a-h. The toxicity and antitumor activities of the synthesized compounds were studied.

Safety of Natural Insecticides: Toxic Effects on Experimental Animals.

Long-term application and extensive use of synthetic insecticides have resulted in accumulating their residues in food, milk, water, and soil and cause adverse health effects to human and ecosystems. Therefore, application of natural insecticides in agriculture and public health sectors has been increased as alternative to synthetic insecticides. The question here is, are all natural insecticides safe. Therefore, the review presented here focuses on the safety of natural insecticides. Natural insecticides contain chemical, mineral, and biological materials and some products are available commercially, e.g., pyrethrum, neem, spinosad, rotenone, abamectin, Bacillus thuringiensis (Bt), garlic, cinnamon, pepper, and essential oil products. It can induce hepatotoxicity, renal toxicity, hematotoxicity, reproductive toxicity, neurotoxicity, and oxidative stress. It can induce mutagenicity, genotoxicity, and carcinogenicity in mammals. Some natural insecticides and active compounds from essential oils are classified in categories Ib (Highly hazardous) to U (unlikely toxic). Therefore, the selectivity and safety of natural insecticides not absolute and some natural compounds are toxic and induce adverse effects to experimental animals. In concussion, all natural insecticides are not safe and the term "natural" does not mean that compounds are safe. In this respect, the term "natural" is not synonymous with "organic" and not all-natural insecticide products are acceptable in organic farmers.

Formulation and characterization of garlic (Allium sativum L.) essential oil nanoemulsion and its acaricidal activity on eriophyid olive mites (Acari: Eriophyidae).

Green and nanoacaricides including essential oil (EO) nanoemulsions are important compounds to provide new, active, safe acaricides and lead to improvement of avoiding the risk of synthetic acaricides. This study was carried out for the first time on eriophyid mites to develop nanoemulsion of garlic essential oil by ultrasonic emulsification and evaluate its acaricidal activity against the two eriophyid olive mites Aceria oleae Nalepa and Tegolophus hassani (Keifer). Acute toxicity of nanoemulsion was also studied on male rats. Garlic EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and the major compounds were diallyl sulfide (8.6%), diallyl disulfide (28.36%), dimethyl tetrasulfide (15.26%), trisulfide,di-2-propenyl (10.41%), and tetrasulfide,di-2-propenyl (9.67%). Garlic oil nanoemulsion with droplet size 93.4 nm was formulated by ultrasonic emulsification for 35 min. Emulsification time and oil and surfactant ratio correlated to the emulsion droplet size and stability. The formulated nanoemulsion showed high acaricidal activity against injurious eriophyid mites with LC50 298.225 and 309.634 µg/ml, respectively. No signs of nanoemulsion toxicity were noted in treating rats; thus, it may be considered non-toxic to mammals. Stability of garlic oil nanoemulsion, high acaricidal activity, and the absence of organic toxic solvents make the formulation that may be a possible acaricidal product. Results suggest the possibility of developing suitable natural nanoacaricide from garlic oil.

Lactational exposure to abamectin induced mortality and adverse biochemical and histopathological effects in suckling pups.

Information about the adverse effects of lactation transfer of abamectin (ABA) is important for human health, especially in the third-world countries where breastfeeding is the only source of nutrition for infants. So, the present study was undertaken to evaluate the adverse effects of breastfeeding exposure to ABA on oxidative damage and liver and kidney dysfunction in suckling rats. Dams were orally administered ABA at a doses 22.10, 11.05, and 2.21 mg a.i./kg b.wt from postnatal day 1 (PND1) until day 20 (PND20). The signs of toxicity and high mortality were recorded in suckling male (67.5%) and female (55.0%) pups whose mother exposed to the ABA at dose 22.1 mg a.i./kg b.wt. ABA induced significantly decrease in body weights of mothers and their male and female pups and significant increase in relative liver weights. It caused oxidative stress in the liver and kidney of mothers and their pups by increasing the level of malondialdehyde (MDA) and decreased activities of superoxide dismutase (SOD) and glutathione-transferase (GST). ABA altered the level of serum liver and kidney dysfunction biomarkers either in the mothers or their male and female pups in a dose-dependent manner. It caused histopathological alterations in the liver and kidney tissues. It can be decided that ABA was accumulated in mother's milk, transferred through breast feeding, and induced mortality in their suckling pups. It caused oxidative stress, lipid peroxidation, and biochemical and histopathological alterations in the liver and kidney of mothers and their suckling pups. The results in the present study add some information about the adverse effect of lactation transfer of ABA, which is important for human health in the third-world countries where breastfeeding may be the only source of nutrition for infants in the first and most critical weeks of life.

Hepatoprotective Efficacy of Cichorium intybus L. Extract Against Carbon Tetrachloride-induced Liver Damage in Rats.

The purpose of the study was to assess the phytochemical and hepatoprotective activity of different extracts of dried herb of Cichorium intybus L. against carbon tetrachloride (CCl4) intoxicated male albino rats. The hepatoprotective activity of different extracts at 500 mg/kg body weight was compared with carbon tetrachloride-treated animals. The animals were divided into five groups with six animals in each group. The first group represents control, the second group received carbon tetrachloride, the third received C. intybus, and the fourth group received C. intybus plus carbon tetrachloride. The fifth group received silymarin as hepato-slandered drug. There were significant changes in serum biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, and γ-glutamyl transferase (GGT) in carbon tetrachloride intoxicated rats, which were restored towards normal values in C. intybus-treated animals. Histopathological examination of liver tissues further substantiated these findings. In conclusion, of this investigation, the results ascertain that the herb extracts of C. intybus possess significant hepatoprotective activity.

Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats.

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg(-1) body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg(-1) body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.

Antioxidant activity and hepatoprotective potential of Cedrelopsis grevei on cypermethrin induced oxidative stress and liver damage in male mice.

BACKGROUND: The liver is the most sensitive and main target organ of pesticide toxicity and damage, they play an essential role in metabolism and detoxification of pesticides. Due to these functions, hepatotoxicity continues to be among the main threats to public health, and they remain problems throughout the world. Therefore, the present study was designed to evaluate the antioxidant and hepatoprotective effects of Cedrelopsis grevei leaves against cypermethrin (Cyp) induced oxidative stress and liver damage in male mice. METHODS: The extracts were subjected to different analyses (phenolics, tannin, flavonoids, antioxidant activity and reducing power assays). For hepatoprotective evaluation, male mice were daily exposed to Cyp and/or C. grevei by gavages for 28 days. Hepatoprotective effects were demonstrated by significant alterations in serum liver dysfunction biomarker enzymes, liver lipid peroxidation and antioxidant enzymes. RESULTS: The antioxidant activity of C. grevei methanolic extract was the highest with an IC50<225 µg/ml by DPPH assay. The high dose of methanolic extract (300 mg/kg. b.wt.) was effective to attenuate the perturbations in the tested enzymes. Histopathological examination in the liver tissue of those mice, demonstrated that a co-administration of methanolic extract (150 & 300 mg/kg/day) showed marked improvement in its histological structure in comparison to Cyp-treated group alone and represented by nil to moderate degree in inflammatory cells. CONCLUSIONS: In view of the data of the present study, it can deduce that cypermethrin caused oxidative damage and liver dysfunction in male mice. C. grevei extract has protective effects on cypermethrin-induced lipid peroxidation, oxidative stress and liver damage. Results indicated that administration of C. grevei is useful, easy, and economical to protect humans against pesticide toxicity. The results presented here can be considered as the first information on the hepatoprotective and antioxidant properties of C. grevei extracts. In a future study, we will identify and investigate the components responsible for the hepatoprotective and antioxidant activities of C. grevei.

Sub-chronic exposure to fipronil induced oxidative stress, biochemical and histopathological changes in the liver and kidney of male albino rats.

Fipronil (FPN) is a broad-spectrum N-phenylpyrazole insecticide and has been used in agriculture and public health since the mid-1990s. The present study was designed to investigate the adverse effects of sub-chronic exposure to the FPN on the liver and kidney of male rats at three concentrations 0.1, 1 and 10 mg/L in drinking water for 45 days. Serum aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity and levels of uric acid, creatinine and total protein were significantly increased in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reduced (GSH) were significantly decreased, while lipid peroxidation (LPO) was significantly increased in treating rats in a concentration dependent manner. FPN caused histopathological alterations in liver and kidney of male rats. From our results, it can be concluded that FPN induced lipid peroxidation, oxidative stress, liver, and kidney injury in rats. These pathophysiological changes in liver and kidney tissues could be due to the toxic effect of FPN that associated with a generation of free radicals.

Antimutagenic effect of Origanum majorana L. essential oil against prallethrin-induced genotoxic damage in rat bone marrow cells.

This study aimed to investigate the genotoxic and cytotoxic potential of prallethrin in rat bone marrow cells and the protective effect of Origanum majorana L. essential oil (EO). Our results demonstrated that prallethrin at dose 64.0 mg/kg body weight (b.wt.) (1/10 LD50), has a clastogenic/genotoxic potential as shown by the high percentage of chromosomal aberration (CA) and micronucleus (MN) in the bone marrow cells of male rats, whereas the combined treatment of prallethrin and O. majorana EO resulted in the reduction of the CA (54.54%). The combined treatment also reduced the micronuclei formation significantly. In conclusion, prallethrin can be considered clastogenic/genotoxic and may carry a risk to human health. The study revealed the antigenotoxic and anticytotoxic potential of O. majorana EO against prallethrin-induced genotoxic and cytotoxic effects in rat bone marrow cells.

Amelioration of prallethrin-induced oxidative stress and hepatotoxicity in rat by the administration of Origanum majorana essential oil.

This study was carried out to evaluate the adverse effects of exposure to prallethrin on oxidant/antioxidant status and liver dysfunction biomarkers and the protective role of Origanum majorana essential oil (EO) in rat. Male rats were divided into 4 groups: (i) received only olive oil (ii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) in olive oil via oral route daily for 28 days, (iii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) and EO (160 µL/kg b.wt.) in olive oil and (iv) received EO (160 µL/kg b.wt.) in olive oil via oral route twice daily for 28 days. Prallethrin treatment caused decrease in body weight gain and increase in relative liver weight. There was a significant increase in the activity of serum marker enzymes, aspartate transaminase, alanine transaminase, and alkaline phosphatase. It caused increase in thiobarbituric acid reactive substances and reduction in the activities of superoxide dismutase, catalase, and glutathione-S-transferase in liver. Consistent histological changes were found in the liver of prallethrin treatment. EO showed significant protection with the depletion of serum marker enzymes and replenishment of antioxidant status and brought all the values to near normal, indicating the protective effect of EO. We can conclude that prallethrin caused oxidative damage and liver injury in male rat and co-administration of EO attenuated the toxic effect of prallethrin. These results demonstrate that administration of EO may be useful, easy, and economical to protect human against pyrethroids toxic effects.

Adverse effects of exposure to low doses of chlorpyrifos in lactating rats.

This study was conducted to shed light on the effect of exposure of lactating rat to chlorpyrifos (CPF). CPF was orally administered to lactating rats at 0.01 mg kg(-1) b.wt. (acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 LD( 50)) from postnatal day 1 (PN1) until day 20 (PN20) after delivery. Results indicated decreases in body weight and increases in relative liver and kidney weights of exposed dams. Significant damage to liver was observed via increased plasma levels of aminotransferases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) lactate dehydrogenase (LDH) and γ-glutamyle transferase (γ-GT) in a dose-dependent manner. At two high doses of CPF (1.00 and 1.35 mg kg(-1) b.wt.), the lactating mothers showed significant decrease in the activity of cholinesterase (ChE). Lipid peroxidation was significantly increased, while glutathione s-transferase (GST) and superoxide dismutase (SOD) were significantly decreased compared to control. At high dose of CPF (1.35 mg kg(-1) b.wt.), total protein and uric acid levels were significantly increased. CPF caused dose-related histopathological changes in liver and kidney of the CPF-treated dams.

Synthesis and antioxidant activity of new pyridines containing gallate moieties.

Pyridines containing the galloyl moiety have been prepared utilizing 4-acetyl pyrogallol. In addition, fused pyridines were synthesized from the obtained pyridines via further chemical transformations. The results indicated that compound 4a showed stronger DPPH scavenging activity than the other compounds, and the scavenging effect decreased in the following order 4a > t-BHQ > 2a > 2b > 3a > 3b > 4b. Accordingly, other antioxidant assays were conducted for 4a. The results suggested that compound 4a could be a good antioxidant candidate. The absence of mortality of rats receiving 5000 mg/kg body weight of 4a as single oral dose may indicate that it could be a safe antioxidant and may be used for further studies.

Effects of methomyl on lipid peroxidation and antioxidant enzymes in rat erythrocytes: in vitro studies.

Erythrocytes are a convenient model to understand the membrane oxidative damage induced by various xenobiotic pro-oxidants. This study was designed to investigate the possibility of methomyl (Lannate 90% SP), S-methyl N-(methylcarbamoyloxy) thioacetimidate, to induce oxidative stress response in rat erythrocytes in vitro. Erythrocytes were incubated for 4 hours at 37 degrees C with different concentrations (0.0, 0.1, 0.5, 1.0, 1.5 and 2.0 mM) of methomyl. The results showed that methomyl decreased acetylcholinesterase (AChE), superoxide dismutase (SOD) and glutathione S-transferase (GST) activities and increased level of lipid peroxidation (LPO) as well as the percentage of haemolysis. The response occurred in a concentration-dependent manner. The study suggested that methomyl has the capability to induce oxidative damage as evidenced by increasing LPO and perturbations in various antioxidant enzymes.