Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers

Abstract

Accidental or intentional ingestion of glyphosate surfactant-based herbicides, like Roundup®, leads to nephrotoxicity as well as death. In this study, a panel of kidney injury biomarkers was evaluated in terms of suitability to detect acute kidney injury and dysfunction. The Roundup®intoxication model involved oral administration of glyphosate to rats at dose levels of 250, 500, 1200 and 2500mg/kg. Urinary and plasma biomarker patterns were investigated at 8, 24 and 48h after dosing. Biomarkers were quantified by absolute concentration; by normalising to urine creatinine; and by calculating the excretion rate. The diagnostic performances of each method in predicting of acute kidney injury were compared. By Receiver Operating Characteristic (ROC) analysis of the selected biomarkers, only urinary kidney injury molecule-1 (KIM-1) best predicted histological changes at 8h (best cut-off point>0.00029μg/ml). Plasma creatinine performed better than other biomarkers at 24h (best cut-off point>0.21mg/dl). Urinary KIM-1 was the best early biomarker of kidney injury in this glyphosate-induced nephrotoxicity model. © 2013 Elsevier Ireland Ltd.