Effect of zinc supplementation on immunotoxicity induced by subchronic oral exposure to glyphosate-based herbicide (GOBARA®) in Wistar rats.

OBJECTIVES: To evaluate the effect of zinc supplementation on immunotoxicity induced by subchronic oral exposure to glyphosate-based herbicide (GBH). METHODS: Sixty adult male Wistar rats randomly divided equally into six groups were exposed to GBH by gavage daily for 16 weeks with or without zinc pretreatment. Group DW rats received distilled water (2 mL/kg), group Z rats received zinc (50 mg/kg), and group G1 and G2 rats received 187.5 and 375 mg/kg GBH, respectively. Group ZG1 and ZG2 rats were pretreated with 50 mg/kg zinc before exposure to 187.5 and 375 mg/kg GBH, respectively. Tumor necrosis factor alpha (TNF-α) and immunoglobulin (IgG, IgM, IgE) levels were measured by enzyme-linked immunosorbent assay. Spleen, submandibular lymph node, and thymus samples were processed for histopathology. RESULTS: Exposure to GBH (G1 and G2) significantly increased serum TNF-α concentrations and significantly decreased serum IgG and IgM concentrations compared with the control levels. Moderate-to-severe lymphocyte depletion occurred in the spleen, lymph nodes, and thymus in the GBH-exposed groups. Zinc supplementation mitigated the immunotoxic effects of GBH exposure. CONCLUSIONS: GBH exposure increased pro-inflammatory cytokine responses, decreased immunoglobulin production, and depleted lymphocytes in lymphoid organs in rats, but zinc supplementation mitigated this immunotoxicity.

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.

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.