Effect of zinc supplementation on chronic hepatorenal toxicity following oral exposure to glyphosate-based herbicide (Bushfire®) in rats.

OBJECTIVES: To assess the effects of zinc pretreatment on hepatorenal toxicity following chronic exposure to glyphosate-based herbicides in male rats. METHODS: Following zinc pretreatment (50 mg/kg and 100 mg/kg), 14.4 to 750 mg/kg of oral glyphosate (Bushfire® herbicide) was administered daily for 36 weeks. Thereafter, serum samples were obtained following jugular venipuncture. Liver and kidney samples were processed for histopathological examination. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity as well as levels of bicarbonate, calcium, creatinine were significantly increased following chronic exposure to Bushfire®. Serum levels of sodium, potassium, chloride, total protein, albumin, globulin and urea were unchanged. Moderate to severe coagulative necrosis of hepatocytes as well as glomerular and renal tubular necrosis were observed in herbicide-treated rats. Zinc pretreatment reduced the elevation of serum enzymes associated with hepatobiliary lesions, abrogated hypercalcemia and metabolic alkalosis, and mitigated serum accumulation of creatinine following Bushfire® exposure, but was ineffective in completely preventing histological lesions. CONCLUSION: Chronic Bushfire® exposure in rats caused hepatorenal toxicity. The effects of exposure on serum parameters were ameliorated by zinc pretreatment, but the histopathological changes associated with toxicity persisted in milder forms in zinc-pretreated animals.

Pancreatic function and histoarchitecture in Wistar rats following chronic exposure to Bushfire®: the mitigating role of zinc.

Objectives To assess the toxicopathologic effects of chronic exposure to the glyphosate-based herbicide Bushfire® on the pancreas of Wistar rats and the protective role of zinc. Methods We exposed the rats to daily doses of 14.4 to 750 mg/kg body weight of the glyphosate-based herbicide Bushfire® and to 50 or 100 mg/kg zinc, and measured blood glucose levels and serum insulin levels. Tissue samples were evaluated for histopathological alterations. Results Levels of both blood glucose and serum insulin increased in glyphosate-exposed rats, and moderate to severe degenerative changes were observed in both glandular pancreatic acinar cells and islets of Langerhans in all rats exposed to glyphosate. These effects were prevented by pretreatment with zinc. Conclusion Chronic exposure to glyphosate can alter pancreatic function and histoarchitecture, but zinc supplementation can mitigate these toxicopathologic effects.

The protective role of alpha-lipoic acid on long-term exposure of rats to the combination of chlorpyrifos and deltamethrin pesticides.

The study was aimed at evaluating the protective role of α-lipoic acid (ALA) on long-term exposure of rats to the combination of chlorpyrifos (CPF) and deltamethrin (DLT). Forty-two (42) male Wistar rats were divided into 6 exposure groups with 7 animals in each group: (I) soya oil (2 ml kg-1), (II) ALA (60 mg kg-1), (III) DLT (6.25 mg kg-1), (IV) CPF (4.75 mg kg-1), (V) (CPF + DLT) DLT (6.25 mg kg-1) and CPF (4.75 mg kg-1; 1/20th of the previously determined median lethal dose) and (VI) (ALA + CPF + DLT) pretreated with ALA (60 mg kg-1) and then co-exposed to CPF and DLT, 45 min later. The regimens were administered by gavage once daily for a period of 16 weeks. Sera obtained from blood collected at the end of the experimental period were used for the evaluation of serum glucose, total protein, albumin, urea, creatinine and the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and acetylcholinesterase. The liver homogenate was used to assay for the activities of superoxide dismutase and glutathione peroxidase and the concentrations of malondialdehyde, cytokine and tumour necrotic factor α. The result showed that the combination of CPF and DLT resulted in marked alterations of these biochemical parameters in most cases compared to either of the pesticides singly, supplementation with ALA ameliorated these alterations.

Influence of zinc supplementation on histopathological changes in the stomach, liver, kidney, brain, pancreas and spleen during subchronic exposure of Wistar rats to glyphosate.

A subchronic toxicity study was carried out to determine the glyphosate-induced histopathological changes in the stomach, liver, kidney, brain, pancreas and spleen of rats and the attendant ameliorative effect when pretreated with zinc at the dose rate of 50 mg/kg body weight. The rats were exposed to two doses of the glyphosate (375 and 14.4 mg/kg body weight) for the period of 8 weeks which was the duration of the study, and some groups were exposed to the glyphosate after pretreatment with zinc. The histopathological changes recorded during the study were only in the rats exposed to the glyphosate at the dose rate of 375 mg/kg body weight except the vacuolation encountered in the brains and haemosiderosis in the spleens of rats exposed to zinc alone. Degenerated mucosal epithelial cells which involved the muscularis mucosa and the glands in the stomachs of rats were seen microscopically. Hepatic cells degeneration especially at the portal areas of the livers of rats was observed. The histopathological examination of the kidneys showed glomerular degeneration, mononuclear cells infiltration into the interstices of the tubules and tubular necrosis. The conspicuous changes seen in the brains were neuronal degeneration. Pancreatic acinar cells were degenerated while the spleen of the rats showed depopulated splenic cells in both the red and the white pulps. It was concluded that zinc supplementation in rats prior to glyphosate exposure ameliorated the histopathological changes observed in the stomach, liver, kidney, brain, pancreas and spleen with no observable alteration in the histoarchitecture in the organs of the zinc-supplemented rats.

Serum biochemical assessment of hepatic and renal functions of rats during oral exposure to glyphosate with zinc.

A subchronic toxicity study was carried out to assess hepatic and renal functions of rats during oral exposure to glyphosate with zinc for the period of 8 weeks. Forty-eight Wistar rats used for the study were randomized into six groups of eight Wistar rats each, and each group had equal number of male and female Wistar rats. The Wistar rats administered with distilled water at 2 ml/kg body weight served as the control group (DW); others were administered with zinc at 50 mg/kg body weight (Z) group, glyphosate at 375 mg/kg body weight (G) group, a combination of zinc and glyphosate at 50 and 375 mg/kg body weight, respectively (Z + G), group, glyphosate at 14.4 mg/kg body weight (GC) group, and a combination of zinc and glyphosate at 50 and 14.4 mg/kg body weight, respectively (Z + GC), group. At the end of the study, blood samples were collected from each rats; from which, sera samples were obtained and assayed for total protein, albumin, alanine and aspartate aminotransferases, alkaline phosphatase, Na+, K+, Cl-, [Formula: see text], Ca2+, [Formula: see text], urea and creatinine using autoanalyzer, and globulin was calculated. The albumin concentration was significantly high (p < 0.05) in GC group compared to DW group, and this change was ameliorated following supplementation with zinc. The total protein and globulin concentrations did not differ significantly between the groups (p > 0.05), and the relative changes were ameliorated by supplementation with zinc. The alkaline phosphatase activity was relatively low in GC group; however, supplementation with zinc in Z + GC group made it to be significantly high (p < 0.05) compared to GC group. The alanine and aspartate aminotransferases in G and GC groups were relatively high compared to DW group, which were ameliorated by supplementation with zinc. The relatively low Ca2+ concentration in G and GC groups compared to DW were ameliorated in Z + G group, and it was significantly high in Z + GC group at p < 0.01 compared to DW, p < 0.001 compared to G and GC groups and p < 0.05 compared to Z + G group. There were only slight changes in the electrolytes concentrations (Na+, K+, Cl-, [Formula: see text] and [Formula: see text]), which were differentially ameliorated by zinc supplementation. The reasons for the various changes recorded were discussed. It was concluded that subchronic oral exposure to glyphosate caused both hepatic and renal functions toxicity in rats, which were ameliorated by zinc supplementation.

Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid.

The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF) and deltamethrin (DLT) on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA) on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil) and II (ALA) were given soya oil (2 ml/kg) and ALA (60 mg/kg), respectively. Rats in group III (DLT) and IV (CPF) were exposed to DLT (6.25 mg/kg) and CPF (4.75 mg/kg) (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h). Rats in group V (CPF + DLT) were co-exposed to CPF (4.75 mg/kg) and DLT (6.25 mg/kg), while those in group VI (ALA + CPF + DLT) were pretreated with ALA (60 mg/kg) and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA) concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

Ameliorative effect of vitamin C on chronic chlorpyrifos-induced erythrocyte osmotic fragility in Wistar rats.

Chronic exposure to chlorpyrifos (CPF) has been shown to cause increased lipoperoxidative changes in the erythrocyte membranes. The relationship between chronic CPF-induced lipoperoxidative changes and erythrocyte fragility has not been elucidated. The aim of the present study is to evaluate the role of lipoperoxidation on CPF-induced erythrocyte fragility and the ameliorative effect of vitamin C. Twenty animals divided at random into four groups of five animals each served as subject for this study. Rats in group I served as the control group and were given only soya oil at a dose of 2 mL/kg body weight (b.w.). Rats in group II were dosed with vitamin C (100 mg/kg b.w.) and then supplemented with soya oil (2 mL/kg b.w.), while those in group III were administered with CPF only at a dose of 10.6 mg/kg b.w. (~one-eighth of the previously determined median lethal dose [LD(50)]). Rats in group IV were pretreated with 100 mg/kg b.w. of vitamin C, and then dosed with CPF at a dose of 10.6 mg/kg b.w., 30 min later. The different treatment regimens were orally administered daily for a period of 17 weeks. Blood collected from the animals at the end of the test period were analyzed for erythrocyte osmotic fragility and malonaldehyde (MDA) concentration as an index of lipid peroxidation. The study showed that CPF caused significant increase in erythrocyte fragility and MDA concentration, which were ameliorated by pretreatment with vitamin C. In conclusion, the study showed that CPF-evoked erythrocyte fragility due to increased lipoperoxidative changes was ameliorated by pretreatment with vitamin C.