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

Abstract

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.

Differential Protective Effect of Zinc and Magnesium for the Hepatic and Renal Toxicity Induced by Acetaminophen and Potentiated with Ciprofloxacin in Rats

“…Pretreatment with zinc chloride (50 or 100 mg/kg daily, 36 days) reduced renal and hepatic toxicity of glyphosate, and ameliorated numerous biochemical parameters (serum accumulation of creatinine), but did not alleviate histological damage in rats [42].…”

“…Their results are reinforced by experimental studies that demonstrated the protective effect of zinc on liver damage induced by D-galactosamine or nickel in rats [40,41]. Pretreatment with zinc chloride (50 or 100 mg/kg daily, 36 days) reduced hepatic toxicity of glyphosate, ameliorated numerous biochemical parameters (such as increases in serum enzymes associated with hepatobiliary injury), but were ineffective in preventing histological lesions [42].…”

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

“…The rats were randomly selected and assigned to six groups (n = 10/group) as follows: group DW (control), each rat was orally administered 2 mL/kg of distilled water daily; group II (Z), each rat was orally administered zinc chloride (2%) at 50 mg/kg; 26 group G1, each rat was orally administered 187.5 mg/kg glyphosate in GBH) (5% of the LD 50 ); 20 group G2, each rat was orally administered 375 mg/kg glyphosate in GBH (10% of the LD 50 ); 20 group ZG1, each rat was orally pretreated with 50 mg/kg zinc chloride 1 hour before the oral administration of 187.5 mg/kg GBH; and group ZG2, each rat was orally pretreated 50 mg/kg zinc chloride 1 hour before the oral administration of 375 mg/kg GBH.…”

“…18 Evidence regarding the immunotoxicity of glyphosate and GBH in animal models is limited, and further investigation is required. 19 Zinc supplementation was used in our previous studies to ameliorate the toxic effects of GBH [20][21][22][23][24][25][26] based on the premise that zinc can enhance anti-oxidant and anti-inflammatory responses. 27 In the present study, we focused on the immunotoxicity of GBH exposure with respect to pro-inflammatory cytokine and immunoglobulin responses and the stability of lymphocyte populations in lymphoid tissues of the spleen, lymph nodes, and thymus.…”

Perinatal Exposure to a Glyphosate Pesticide Formulation Induces Liver Damage in Immature Rat Pups

“…It is widely recognized that the liver is the major organ affected by xenobiotic exposure, and, experimental studies have demonstrated that exposure to GBH or glyphosate itself may have a hepatotoxic potential and may cause liver injury (Soudani et al 2019;Milić et al 2018; Mesnage et al 2017;Tizhe et al 2020). A previous study demonstrated that chronic ultra-low dose of Roundup® leads to rat liver and kidney damage (Mesnage et al 2015).…”