A two generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate after gestational and lactational exposure in female Wistar rats

Polychlorinated biphenyls and diethyl phthalate are both lipophilic in nature and are likely to be present in the same environmental compartment or bioaccumalate over a period of time, thus a mixture toxicity study was undertaken to evaluate the type of interaction between polychlorinated biphenyls (Clophen A60) and diethyl phthalate over two generations in female Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100 g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed on normal diet and water ad libitum. Group II male and female rats were maintained on normal diet mixed with corn oil as oil control. GroupS III and IV male and female rats were given Clophen A60 and diethyl phthalate dissolved in corn oil mixed with the diet at 50 mg/kg of the diet individually to each group. Group V male and female rats received a mixture of diethyl phthalate and Clophen A60, each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet. Hundred days after the treatment, females were mated with the males in each group for 10 days. Exposure to diethyl phthalate and Clophen A60 was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation female rats. Treatment for F1 generation male and female pups (6 males & 6 females) with Clophen A60 and diethyl phthalate individually and in mixture was continued at doses reduced to 25 mg/kg of the diet after they reached 75-100 g in weight. The treatment was carried out similar to the parental generation for a period of 150 days. Liver and serum aspartate aminotransferase, liver cholesterol and glycogen were significantly increased in the F1 generation Clophen A60 + diethyl phthalate treated group, whereas serum cholesterol, liver glutathione and glutathione reductase showed a significant decrease in the F1 generation Clophen A60 + diethyl phthalate treated group as compared to the parental generation mixture and individually treated groups as well as the individually treated F1 generation groups. A significant increase was observed in the liver and serum aspartate aminotransferase activity of Clophen A60 and serum aspartate aminotransferase levels of diethyl phthalate treated F1 generation rats as compared to the parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Liver glutathione levels were significantly decreased in the F1 generation Clophen A60 and diethyl phthalate individually treated rats which was similar to the parental generation individually treated rats as compared to the controls. Liver glutathione reductase level was also significantly declined in the diethyl phthalate treated F1 individual group as compared to diethyl phthalate individually treated parental generation rats. Histology of the liver showed fatty degeneration in the mixture treated F1 generation rats as compared to Clophen A60 and diethyl phthalate individually treated F1 rats and parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Thus, in spite of dose reduction and continuous exposure over two generation’s to a mixture of diethyl phthalate and Clophen A60 exposed through gestation, lactation and diet leads to a synergistic toxic effect in the F1 generation.     

Dose-dependent sub-chronic toxicity of diethyl phthalate in female Swiss mice

The experiment was conducted to study the after effects of administering DEP at different doses to female Swiss mice for a period of 90 days. Group I mice were fed on normal diet and water ad libitum. Group II mice were maintained on normal diet mixed with corn oil at 8.25 mg/kg of the diet/day as oil control. Group III, IV and V mice were given diethyl phthalate dissolved in corn oil mixed with the diet at 10, 25 and 50 mg/kg of the diet/day, which is approximately equal to 1.25, 3.125 and 6.25 mg/kg body weight/day. A significant dose dependent increase was observed in serum acid phosphatase (ACP) whereas, serum and liver triglycerides levels showed a significant increase only in the high-dose treated group. Significant dose-dependent increase in serum aspartate and alanine aminotransferase (AST and ALT) and liver glycogen was observed. Serum lactate dehydrogenase (LDH) was significantly increased only in 25 and 50 ppm DEP-treated mice. Liver cholesterol was significantly increased in all the treated groups. Liver histology by light microscopy showed intracellular vacuolations in all the treated groups which was much more evident in the 25 and 50 ppm DEP-treated mice while hepatocellular degeneration and hypertrophy of the hepatocytes was evident in 50 ppm DEP-treated mice. Proliferation of mitochondria and peroxisomes was evident in the electron micrographs of the 10 ppm DEP-treated mice while 25 and 50 ppm DEP-treated mice showed increase in lipid droplets and severe mitochondrial proliferation.     

Ameliorative effect of lycopene on antioxidant status in Cyprinus carpio during pyrethroid deltamethrin exposure

The aim of the present study was to investigate the ameliorative properties of lycopene against the toxic effects of deltamethrin (DM) by examining oxidative damage markers such as lipid peroxidation and the antioxidant defense system components in carp (Cyprinus carpio). The fish were divided into seven groups of 15 fish each and received the following treatments: Group 1, no treatment; Group 2, orally administered corn oil; Group 3, oral lycopene (10 mg/kg body weight); Group 4, exposure to 0.018 μg/L DM; Group 5, exposure to 0.018 μg/L DM plus oral administration of 10 mg/kg lycopene; Group 6, exposure to 0.036 μg/L DM; and Group 7, exposure to 0.036 μg/L DM plus oral administration of 10 mg/kg lycopene. Treatment was continued for 14 days, and at the end of this period, blood and tissue (liver, kidney, and gill) samples were collected. Levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were determined in blood and tissues for measurement of oxidant-antioxidant status. A significant elevation in the level of MDA, as an index of lipid peroxidation, and reductions in antioxidant enzyme activities (SOD, CAT, and GSH-Px) and low molecular weight antioxidant (GSH) levels were observed in DM-exposed fish. Treatment with lycopene attenuated the DM-induced oxidative stress by significantly decreasing the levels of MDA. In addition, lycopene significantly increased the SOD, CAT, and GSH-Px activities and the level of GSH. The present results suggest that administration of lycopene might alleviate DM-induced oxidative stress.     

Modulation of ethion-induced hepatotoxicity and oxidative stress by vitamin E supplementation in male Wistar rats

Organophosphorus insecticides (OPIs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system of animals. Many studies reported that enzymatic and non-enzymatic antioxidant may play protective role against OPIs induced toxicity in human and rats. The aim of present study was to investigate the possible protective role of vitamin E on ethion-induced hepatotoxicity in rats using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups; each group consists of six animals. Animals were treated for a period of 28 days. Group I (control group received corn oil); Group II [ethion treated (2.7 mg/kg bw/day)]; Group III (vitamin E treated (50 mg/kg of bw/day)]; Group IV (ethion + vitamin E treated). Animals were sacrificed after 7, 14, 21 and 28 days by decapitation and liver tissue was used for the measurement of proteins, lipid peroxidation (LPO), reduced glutathione (GSH) content and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST). Erythrocytes were analyzed for acetyl cholinesterase activity. The result of this study shows that in vivo administration of ethion caused a significant induction of oxidative damage in liver tissue as evidenced by increased level of LPO and decreased GSH content. Ethion toxicity also led to a significant increase in the activities of SOD, CAT, GPx and GST in liver tissue. In addition, decrease in GR activity was observed in ethion administered rats compared to control. Histopathological findings revealed that exposure to ethion caused damage in liver tissue. However, simultaneous supplementation with vitamin E restored these parameters partially. In conclusion, the results of the current study revealed that ethion-induced toxicity caused lipid peroxidation, alterations in the antioxidant enzymes and histopathological changes in liver. Supplementation of vitamin E exhibited protective effect by inhibiting ethion-induced toxicity in liver and erythrocytes.     

Subacute oral toxicity of chlorpyriphos and protective effect of green tea extract

This paper reports the effect of green tea administration following subacute toxicity caused by exposure to organophosphorus pesticide chlorpyriphos in liver of rats. Four groups containing five male Sprague-Dawley rats each were selected. Group I served as control. Group II rats were permitted free access to solubilised crude extract of green tea (1.5%w/v in water) as the sole drinking fluid. Group III rats were given a single daily oral dose of chlorpyriphos (30 mg/kg bodyweight in corn oil). Group IV rats received oral dose of pesticide and green tea extract simultaneously. All rats were sacrificed after 15 days. Significant damage to liver was observed via increased serum levels of transaminases and alkaline phosphatase. Lipid peroxidation showed a 5-fold increase in pesticide exposed rats compared to control. In contrast, levels of antioxidant GSH, glutathione-dependent enzymes like glutathione peroxidase (GPx), glutathione S-transferase (GST) and free radical scavengers like catalase (CAT) and superoxide dismutase (SOD) were significantly lower than those of the control group reinforcing oxidative damage. The use of green tea extract appeared to be beneficial to rats, although not to a great extent in significantly reducing and reversing the damage sustained by pesticide exposure and favors recovery.     

Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats

Pesticides induce oxidative stress leading to generate free radicals and alternate the antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the oral toxicity of chlorpyrifos toward male rat and the oxidative stress of the sub-lethal dose (9 mg/kg; 1/25 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities of testicular tissue. Also, the protective effects of propolis extract (50 mg/kg b.w.) alone or in combination with chlorpyrifos were investigated. The oral administration of chlorpyrifos significantly caused elevation in LPO level by 1.79-fold as compared to control. The activities of antioxidant enzymes including CAT, SOD, GPx and GST were decreased significantly (23.66%, 27.75%, 29.13% and 11.52%) as well as the level of GSH decreased by 21.97% in testicular tissue as compared to control animals. Co-administration of propolis extract with chlorpyrifos or alone in male rats decreased LPO level, normalized CAT, SOD GPx and GST activities, while GSH content was increased in testicular tissue. We conclude that propolis extract significantly reduces chlorpyrifos-induced oxidative stress in rat testis and the protective effect of the pre-treatment with propolis extract as attenuating agent could be due to its antioxidant properties.     

Determination of toxicity of trichloroacetic acid in rats: 50 days drinking water study

This study aims to investigate the effects of the trichloroacetic acid (TCA) on serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation content (Malondialdehyde, MDA) in various tissues of rats. TCA (2000 ppm) as drinking water was administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days continuously. TCA treatments caused different effects on the serum marker enzymes, antioxidant defense systems and the MDA content in experimented rats compared to controls. Results showed that TCA caused a significant increase in serum AST, ALT, CPK and ACP activity. The lipid peroxidation end product MDA slightly increased in the erythrocytes, liver and kidney of rats treated with TCA, whereas did not change in the brain. In addition, antioxidant enzyme activity such as CAT and SOD significantly increased in the brain, liver and kidney tissues of TCA induced group whereas the ancillary enzyme GR and the drug metabolizing enzyme GST activity did not significantly change in the all tissues. The observations presented led us to conclude that the administration of subchronic TCA promotes lipid peroxidation content, elevates tissue damage serum marker enzymes and fluctuates in the antioxidative systems in rats. Also the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat’s tissues. These data, along with the determined changes suggest that TCA produced substantial systemic organ toxicity in the erythrocyte, liver, brain and kidney during the period of a 50-day subchronic exposure.     

Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions

Propoxur (PPr) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Because of the widespread use of pesticides for domestic and industrial applications, evaluation of their neurotoxic effects is of major concern to public health. The aim of the present study was to evaluate the possible protective effects of Nigella sativa oil (NSO), an antioxidant agent, against PPr-induced toxicity and oxidative stress in different brain regions of rats including cerebellum, cortex and hippocampus. In the present study, 32 male Sprague-Dawley rats were used and divided into four equal groups. Group 1 was allocated as the control group. Groups 2-4 were orally administered 1 ml/kg/bw/day NSO, 8.51 mg/kg/bw/day PPr or NSO plus PPr, respectively, for 30 days. Lipid peroxidation (LPO), protein carbonyl content (PCC) and acetylcholine esterase activity (AChE) were determined. Enzymatic antioxidant activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST)] and non-enzymatic antioxidants [reduced glutathione (GSH)] were determined. PPr treatment significantly increased the levels of LPO, PCC and oxidized glutathione (GSSG) in brain regions. On the contrary, levels of GSH and the activities of SOD, CAT, GSH-Px, GST and AChE were significantly decreased. NSO treatment to PPr intoxicated rats restored such biochemical parameters to within control levels except GST activity, emphasizing its antioxidant role. We conclude that NSO significantly reduces PPr-induced toxicity and oxidative stress in rat brain regions via a free radicals scavenging mechanism.     

Effect of α tocopherol and selenium on antioxidant status, lipid peroxidation and hepatopathy induced by malathion in chicks

The objective of the present study was to investigate the role of α tocopherol and selenium on malathion induced hepatic damage, and antioxidant defense in chicks. The chicks were divided into three groups. First group received malathion 10 mg/kg BW, orally for 60 days, the second group received the same dose of malathion but was supplemented with α tocopherol and selenium for 60 days and the third group served as the control. A compromised antioxidant capacity as evidenced by increased levels of erythrocytic lipid peroxidation and decreased concentration of vitamin E and decreased activity of glutathione peroxidase was observed in chicks following the administration of malathion. An improved antioxidant status was observed in chicks of second group with α tocopherol and selenium supplementation including higher concentration of vitamin E, increased activity of glutathione peroxidase and lower levels of lipid peroxidation. Histopathological studies of liver in the chicks which received malathion exhibited, moderate to severe degenerative and necrotic changes in the hepatocytes. The correlation of decreased antioxidant status of chicks with degenerative changes in liver suggests that lipid peroxidation may be one of the important mechanism in the chronic toxicity of malathion. The results indicate that α tocopherol and selenium were effective in partially alleviating degenerative changes induced by malathion in the liver of chicks by attenuating processes leading to lipid peroxidation.     

Effects of indoleacetic acid and kinetin on lipid peroxidation and antioxidant defense in various tissues of rats

This study aims to investigate the effects of indoleacetic acid (IAA) and kinetin (Kn), which are plant growth regulators (PGRs), on antioxidant defense systems [reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT)], and lipid peroxidation level (malondialdehyde, MDA) various tissues of rats. Rats (Sprague-Dawley albino) were exposed to 100 ppm IAA and Kn. One hundred parts per million of PGRs was administered orally to rats ad libitum for 21 days continuously. The PGRs treatments caused different effects on the content of MDA and antioxidant defense system in comparison to those of control rats. According to the results, the subchronic treatments of IAA caused significant decrease in the GSH concentration and CAT activity in erythrocyte. Kn decreased GSH concentration in erythrocyte too. While the MDA concentration in brain was increased significantly by IAA and Kn, Kn decreased significantly brain CAT and GST activity. The liver GST activity was decreased by IAA and Kn. But, liver CAT activity was increased by IAA. On the other hand, while IAA treatment caused a significant decrease kidney GST activity, Kn caused a significant decrease both kidney GST and CAT activity. Also, while heart CAT activity was decreased by IAA, heart GST activity was decreased by both IAA and Kn. Moreover, MDA concentration in heart was increased by Kn treatment. It was concluded that IAA might effect MDA and antioxidant defense on the animals at subchronic treatment.     

Dimethoate induced biochemical perturbations in rat pancreas and its attenuation by cashew nut skin extract

The significant antiradical activity of cashew skin extract was previously described. In this investigation, the extent of protection offered by cashew nut skin extract (CSE) against the damage induced in rat pancreas by sub chronic doses dimethoate (DM), an organophosphorous pesticide was studied. Rats were supplemented with CSE at 20 mg/kg b.w./d after a daily dose of DM at 40 mg/kg/d b.w. for 2 months. Weekly random blood glucose, oral glucose tolerance test (OGTT); pancreatic damage markers like amylase and lipase; oxidative damage markers such as reactive oxygen species generated, extent of lipid peroxidation, host antioxidant defenses like reduced glutathione (GSH); GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR); free radical scavenger enzymes viz., catalase and superoxide dismutase (SOD); xenobiotic metabolizing enzymes like DT-diaphorase and NADPH-diaphorase were measured in the four different groups namely (1) control, (2) DM treated, (3) CSE supplemented, (4) CSE supplements following DM treatment. Random blood glucose levels increased significantly on exposure to DM compared to that in control rats (119 ± 5 mg/dl vs. 92 ± 4 mg/dl), while the blood glucose levels in CSE supplemented rats were comparable to that of controls. DM treated rats exhibited impaired glucose tolerance at the end of two months as indicated by OGTT, while DM treated rats with CSE supplements showed normal glucose tolerance. Pancreatic specific marker enzymes like amylase and lipase in serum were restored to normalcy in rats supplemented with CSE following treatment with DM which otherwise was increased in the DM treated rats. Distinctly lower levels of GSH, increased levels of ROS, higher extent of lipid peroxidation, along with alterations in antioxidant enzymes and increase in xenobiotic metabolizing enzymes were evident in pancreas of DM treated rats. However, CSE supplement ameliorated the biochemical alterations in the pancreatic milieu in DM treated rats. Treatment with CSE significantly protected rat pancreas from injury, thus ameliorating and restoring tissue antioxidant status and also conferring normal glucose tolerance. The active components present in cashew skin extract can perhaps be effective in reducing the extent of pancreatic injury and in overcoming tissue damage caused by exposure to dimethoate.     

Effects of thiacloprid, deltamethrin and their combination on oxidative stress in lymphoid organs, polymorphonuclear leukocytes and plasma of rats

Deltamethrin and thiachloprid are an α-cyano class pyrethroid and neonicotinoid insecticide, respectively. Recently, a pesticide combining deltamethrin and thiacloprid has also been released. In the present study, the acute and subacute toxic effects of deltamethrin, thiachlopride, and a combination of these insecticides, on the lymphoid organs (spleen, thymus and bone marrow), polymorphonuclear leukocytes (PMNs) and plasma of rats, were determined to better understand mammalian antioxidant-oxidant and inflammatory system responses. For this purpose, rats were treated orally with different doses of thiacloprid (single acute dose of 112.5 mg/kg); subacute dose of 22.5 mg/kg/day for 30 days; deltamethrin (single acute dose of 15 mg/kg); subacute dose (3 mg/kg/day for 30 days), or a combination of these pesticides. Results were compared with those from a comparable dosing regimen with the known immunosuppressive drug cyclophosphamide. Pesticide treatments caused significant changes in the levels of liver and kidney injury markers. Antioxidant enzyme (catalase and glutathione peroxidase), glutathione and plasma antioxidant levels decreased but lipid peroxidation increased in all lymphoid organs and the plasma. Glutathione-S-transferase and especially DT-diaphorase activity, decreased after thiacloprid treatment. Myeloperoxidase activity, carbonyl content, lipid peroxidation and total nitrite levels increased in PMNs and plasma. When evaluated as a whole, the oxidative and inflammatory stresses seen in the pesticide combination groups were not much more pronounced than in the groups treated with a single pesticide. In terms of the evaluated biochemical parameters, the pesticides showed similar effects to cyclophosphamide.     

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD₅₀ of DZN (16.25 mg/kg b.w.) or ½ LD₅₀ of DZN; 32.5 mg/kg b.w) or ¼ LD₅₀-DZN + vitE or ½ LD₅₀ + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.     

Influence of subacute and subchronic treatment of abcisic acid and gibberellic acid on serum marker enzymes and erythrocyte and tissue antioxidant defense systems and lipid peroxidation in rats

This study describes the subacute and subchronic effects of two plant growth regulators (PGRs) [abcisic acid (ABA) and gibberellic acid (GA₃)] on serum marker enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), γ-glutamil transpeptidase (GGT)], antioxidant defense systems [reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation level (Malondialdehyde = MDA) in various tissues of rats. Rats (Sprague-Dawley albino) were exposed to 75 ppm (parts per million) of ABA and GA₃. Seventy-five parts per million of PGRs as drinking water was administered orally ad libitum for 25 and 50 days continuously. The PGRs treatments caused different effect on the serum marker enzymes, antioxidant defense systems and the content of MDA in comparison to those of control rats. Results show that ABA caused a significant decrease in serum LDH and CPK activity with both periods. Also, GA₃ significantly decreased serum AST, CPK, and LDH activity with subacute and decreased serum ALT, CPK, LDH, and GGT treated with subchronic periods. The lipid peroxidation end product MDA significantly increased in the erythrocyte, liver, brain, and muscle of rats treated with both the period of GA₃ without significantly change in the erythrocyte and muscle of rats treated with the subacute period of ABA. The GSH levels were significantly depleted in the erythrocyte and brain of rats treated with both the period of GA₃ without any change in the erythrocyte, liver, brain, and muscle of rats treated with both the period of ABA. Also GSH levels in the muscle significantly depleted with the subchronic period of GA₃. Antioxidant enzyme activities such as SOD significantly decreased in the erythrocyte, liver and brain tissues but increased in the muscle tissue of rats treated with both the periods of GA₃. Meanwhile, SOD significantly decreased in liver and brain, and increased in muscle of rats treated with both the period of ABA. While CAT significantly decreased in the all tissues of rats treated with both the period of GA₃, decreased in the liver and muscle of rats treated with both the periods of ABA too. On the other hand, the ancillary enzyme GPx and GR activity in the erythrocytes, liver, brain and muscle were either significantly depleted or not changed with two periods of PGRs. The drug metabolizing enzyme GST activity significantly decreased in the brain of rats treated with subacute period of PGRs but increased in the erythrocytes of rats treated with subacute period of GA₃. As a conclusion, ABA and GA₃ had significantly increased the activity of hepatic damage enzymes. Also the rats resisted to oxidative stress via antioxidant mechanism. However, the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat’s tissues. These data, along with changes, suggest that PGRs produced substantial systemic organ toxicity in the erythrocyte, liver, brain, and muscle during the period of a 25-day subacute and 50-day subchronic exposure.     

Protective role of propolis against reproductive toxicity of chlorpyrifos in male rats

Chlorpyrifos (CPF) is causing different toxicity and propolis has been reported to be an effective antioxidant. Therefore, the present study is aimed to elucidate the possible protective effects of propolis in alleviating the toxicity of chlorpyrifos on reproductive performance, testosterone levels, enzyme activities and lipids profile in serum of male rats. Animals were divided into four groups; one orally administered (o.d.) CPF at a dose of 9 mg/kg b.w. for consecutive 70-days, propolis group (50 mg/kg b.w.), propolis and chlorpyrifos group and a control group. Results showed that there was a correlation between CPF administration and the significant decrease of the sperm counts, spermatozoon survival and testosterone level as well as increase of sperm aberrations. CPF increased significantly the lipid profile and the levels of various serum liver marker enzymes. In contrast, co-administration of propolis to CPF-treated rats restored almost most of these biochemical parameters to normal levels. On the other hand, CPF resulted in histopathological alterations in testes of male rats. However, pre-administration of propolis to CPF-treated animals improved the testicular damage and alleviates the toxic effects of CPF on reproductive functions in male rats.     

Nonthiol ACE inhibitors, enalapril and lisinopril are unable to protect mitochondrial toxicity due to paraquat

Angiotensin-converting enzyme inhibitors (ACEi) were shown to ameliorate endothelial dysfunction in various human diseases and some of these inhibitors have been reported to enhance antioxidant defenses. The objective of the present study was to shown the abilities of enalapril and lisinopril as two nonthiol ACEi on mitochondrial toxicity due to paraquat. In this study, mitochondrial isolation from rat liver was divided into six groups. Group 1 was considered as control, group 2 received paraquat (5 mM), group 3 received enalapril (0.25 mM), group 4 received lisinopril (0.01 mM), group 5 received paraquat (5 mM) + enalapril (0.25 mM), and group 6 received paraquat(5 mM) + lisinopril (0.01 mM). Viability, lipid peroxidation, catalase activity, GSH (reduced glutathione) and GSSG (oxidized glutathione) concentrations were also determined. Simultaneous treatment of mitochondria with enalapril (0.25 mM) + paraquat (5 mM) and lisinopril (0.0.01 mM) + paraquat (5 mM) did not significantly ameliorate the mitochondrial toxicity induced by paraquat (5 mM) alone (p > 0.05). However, the nonthiol ACEi, enalapril showed to partially improve target of lipid peroxidation due to paraquat. In conclusion, nonthiol ACEi treatment did not improve the increased oxidative stress and the decreased antioxidant mechanisms.     

Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc

The protective effects of zinc on liver and kidney injury induced by chlorpyrifos (CPF) were investigated in rats. Male and female rats were orally administered CPF at a dose of 6.75 mg kg⁻¹ body weight for 28 consecutive days. An additional CPF group received zinc (227 mg l⁻¹) in drinking water throughout the experimental duration. Two groups more served as controls. Administration of CPF resulted in a significant increase in serum lipid peroxidation (LPO) level, while induced significant decreases in the activities of plasma superoxide dismutase (SOD), glutathione-S-transferase (GST) and serum acetylcholinesterase (AChE) either in male or female rats. Similarly, a significant increase in the levels of various serum marker enzymes [e.g. aminotransferases (AST and ALT), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT)] and increase the level of total protein, uric acid and creatinine. In contrast, co-administration of zinc to CPF-treated animals restored most of these biochemical parameters to within normal levels. In case of AChE, supplementation of zinc showed little alteration in the activity of this enzyme especially in male rats treated with CPF. CPF caused histopathological change in liver and kidneys of male and female rats. However, zinc administration to CPF-treated animals resulted in overall improvement in liver and kidneys damage, emphasizing its antioxidant role. In light of the available data, it can deduce that CPF-induced lipid peroxidation, oxidative stress, liver and kidneys damage in male and female rats, and conjunction supplementation of zinc has resulted in pronounced ameliorating effect.     

Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phosphorodithioate) and Ethanol in antioxidant status of liver and kidney of experimental mice

Organophosphorus insecticides and ethanol individually cause free radical production induced by oxidative stress and alter the antioxidants and scavengers of free radicals. The present study indicates the effect caused by dimethoate in combination with ethanol on antioxidant status in mice. Daily, dimethoate at a dose of 18 mg/kg body weight and ethanol at 1 g/kg body weight were orally administered concurrently in a subacute study for 14 days. After the experimental period, the liver and kidney homogenates were analysed for various antioxidant enzymes. The results compared with dimethoate alone treated control indicated an increase in hepatic cytochrome P450 and lipid peroxidation. Decrease in superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione in liver was observed. In kidney, decrease in CAT, SOD, GR, GST, and GSH was observed. Acetyl cholinesterase activity of RBC was increased. No significant change was observed in catalase in liver and glutathione peroxidase in kidney. The results of the study allow us to hypothesize that dimethoate along with ethanol disturbs the antioxidant status.     

Effects of N-acetylcysteine on oxidative responses in the liver of fenthion exposed Cyprinus carpio

The aim of this study was to evaluate the effects of different N-acetylcysteine doses on the tolerance to fenthion-induced oxidative stress, alterations in glutathione metabolism and cholinesterase specific activities in the liver by using freshwater fish Cyprinus carpio (Cyprinidae) as a model organism. An acute toxicity study was carried out to determine 96-h median lethal concentration of fenthion for this species (2.16 mg/L) and 80% of this concentration was applied in toxicity studies. Four groups, each containing eight fish were constituted as follows: Control group, fenthion treated group, 0.5 or 400 mg/kg NAC-injected + fenthion-treated groups. Biochemical analyses were carried out spectrophotometrically. Fenthion treatment significantly decreased total glutathione and glutathione levels, glutathione/glutathione disulfide ratio together with glutathione reductase and γ-glutamylcysteine synthetase specific enzyme activities. The higher dose of N-acetylcysteine increased the toxic effects of fenthion and γ-glutamyl transpeptidase specific activity while decreasing glutathione S-transferase specific activity. However, injection of the lower dose provided a limited protection against fenthion toxicity. In all exposure groups, lipid peroxidation increased and total protein levels decreased, while protein depletion was prevented by low dose of N-acetylcysteine application. Acetylcholinesterase and butyrylcholinesterase activities were at similar levels in the liver of C. carpio. A dose-dependent inhibition was observed in butyrylcholinesterase activity by N-acetylcysteine application. The results showed that fenthion had a significant oxidative stress inducing potential through the reduction of glutathione redox capacity. The critical point for overcoming oxidative stress by N-acetylcysteine in fenthion toxicity was the selection of the dose; N-acetylcysteine exerted its toxic effects by means of oxidative stress in fish liver at the higher dose.