[Glutathione and enzymes associated with glutathione metabolism in adriamycin nephropathy]

Recent data have shown the protective effect of thiol groups on the progression of adriamycin-induced experimental nephropathy, in which reactive oxygen metabolites have been postulated to play an important role. To gain greater insight in the role of glutathione (GSH) in adriamycin-induced nephrosis, we studied changes in reduced GSH level and its associated enzymes in kidney tissue of rats undergoing chronic renal failure produced by i.v. infections of adriamycin (2 x 2 mg/kg b.w.). Kidney damage was characterized by increases in relative kidney weight and BUN levels. The results obtained revealed a 15% drop in renal GSH level in adriamycin-treated animals associated by a similar decrease in the gamma-glutamylcysteine synthetase activity. The activities of kidney glutathione reductase (GR) and glutathione peroxiase (GSH-Px) which are critical constituents of GSH-redox cycle, were significantly decreased (23 an 26%, respectively) in response to adriamycin treatment. Rat kidney glutathione-S transferase and gamma-glutamyl transpeptidase activities were not affected in adriamycin induced nephrosis. We propose that the impairment of renal antioxidant defense, characterized by combined drop in GSH, GR and GSH-Px levels, could permit enhanced free radical induced kidney damage in adriamycin-induced nephropathy.