Investigation of regional glutathione levels in a model of chemically-induced renal papillary necrosis

The effect of diphenylamine on renal cortical, outer medullary and inner medullary glutathione (GSH) concentrations and the effect of GSH depletion on the nephrotoxicity of diphenylamine were investigated in male Syrian hamsters. A dose-dependent decrease in renal cortical GSH was observed within 1 hr of a single oral dose of diphenylamine (200, 400 or 600 mg/kg body weight), but statistically significant changes in outer medullary or papillary GSH were not observed. Reduction of renal papillary GSH to 29% of basal concentration [by prior treatment with l-buthionine sulfoxime (500 mg/kg body weight, ip)] did not increase the papillotoxicity of a non-toxic dose of diphenylamine (400 mg/kg) administered orally. The findings indicate that diphenylamine-induced renal papillary necrosis in the Syrian hamster is not associated with a decrease in renal papillary or outer medullary GSH nor mediated by oxidative cell injury.