Comparative Assessment on Mechanism Underlying Renal Toxicity of Commercial Formulation of Roundup Herbicide and Glyphosate Alone in Male Albino Rat

Abstract

There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate. We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat. Fifty-six adult male rats randomized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3.6, 50.4, and 248.4 mg/kg body weight (bw) of glyphosate concentrations for 12 weeks with distilled water administered to the control group. Kidney biomarker (serum urea and creatinine, plasma cystatin-C, and neutrophil gelatinase-associated lipocalin), oxidative stress indices in the kidney tissue, activities of kidney membrane-bound enzymes (Mg-adenosine triphosphatase [ATPase], Ca-ATPase, Na/K-ATPase, and total ATPase), and histopathological changes in the kidney were monitored. Glyphosate concentration in the kidney was quantified by high-performance liquid chromatography with ultraviolet detection. Significant ( P < 0.05) alterations in the levels of the kidney biomarker, oxidative stress markers, and membrane-bound enzymes were observed in the rats exposed to Roundup compared to the rats exposed to glyphosate alone. Rats exposed to Roundup accumulated more glyphosate residue in their kidney tissue. Severe histopathological lesions were only seen in the kidneys of rats exposed to Roundup. The nephrotoxicity observed cannot be due to the active ingredient in the Roundup formulation, as glyphosate alone has virtually no effect on the renal function of the exposed animals. Therefore, the general claim attributing nephrotoxicity of a glyphosate-based herbicide to its active ingredient should be discouraged.

Activation of the N‐methyl‐d‐aspartate receptor is involved in glyphosate‐induced renal proximal tubule cell apoptosis

“…In an acute exposure model (Wunnapuk et al, ), necrotic and apoptotic cells were shown to be primarily located in the tubular epithelium of the proximal straight tubule at 48 hours after exposure. Tubular necrosis was also shown in 12‐week and 60‐day exposure models (Dedeke et al, ; Hamdaoui et al, ). However, glyphosate‐based herbicides such as Roundup contain a mixture of 15% polyoxyethylene amine with other unspecified surfactants (Howe et al, ); as such, its formulation was reported to be more toxic than glyphosate alone (Dedeke et al, ; Gasnier et al, ).…”

“…Tubular necrosis was also shown in 12‐week and 60‐day exposure models (Dedeke et al, ; Hamdaoui et al, ). However, glyphosate‐based herbicides such as Roundup contain a mixture of 15% polyoxyethylene amine with other unspecified surfactants (Howe et al, ); as such, its formulation was reported to be more toxic than glyphosate alone (Dedeke et al, ; Gasnier et al, ). Therefore, whether glyphosate has renal toxicity remains a question.…”

“…There are some epidemiological studies suggesting a potential relationship between glyphosate‐based herbicides (together with other factors) and chronic kidney disease of unknown etiology (CKDu) (Jayasumana, Gunatilake, & Senanayake, ; Jayasumana et al, ; Peraza et al, ). Several studies using models of acute or subchronic exposure as well as long‐term exposure have indicated that the kidney may be one of the main targets of glyphosate, and the renal proximal tubule may be a main target site for glyphosate‐based herbicides (Dedeke, Owagboriaye, Ademolu, Olujimi, & Aladesida, ; Hamdaoui et al, ; Mesnage et al, ; Tizhe et al, ; Wunnapuk et al, ). However, some studies have suggested that the formulation of herbicides is more toxic than glyphosate alone (Dedeke et al, ; Gasnier et al, ).…”

“…Several studies using models of acute or subchronic exposure as well as long‐term exposure have indicated that the kidney may be one of the main targets of glyphosate, and the renal proximal tubule may be a main target site for glyphosate‐based herbicides (Dedeke, Owagboriaye, Ademolu, Olujimi, & Aladesida, ; Hamdaoui et al, ; Mesnage et al, ; Tizhe et al, ; Wunnapuk et al, ). However, some studies have suggested that the formulation of herbicides is more toxic than glyphosate alone (Dedeke et al, ; Gasnier et al, ). Therefore, whether glyphosate alone could impair renal function and how glyphosate targets the renal proximal tubule should be explored.…”

A comprehensive analysis of the animal carcinogenicity data for glyphosate from chronic exposure rodent carcinogenicity studies

“…They also saw degeneration in the tubulur epithelial cells and expansion and vacuolar degeneration in glomerulus Bowman's capsule (p < 0.05 for both). Dedeke et al [47] also saw significant changes in MDA, GSH and several other kidney biomarkers from exposure to the GBH Roundup in male albino rats. They also studied glyphosate alone in equal doses to the GBH and saw smaller, but still significant increases in MDA and GSH, but not in the other biomarkers.…”