Changes in glutathione peroxidase system and pyridine nucleotide phosphate levels in kidneys of cephaloridine-administered rats.

Abstract

To elucidate the nephrotoxic mechanisms of cephaloridine (CER), changes in renal contents of glutathione (GSH), glutathione disulfide (GSSG), reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH and NADP) and changes in renal activities of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were examined for 15 days in rats that received single intravenous injections of CER in doses of 0 (control), 100 and 1,000 mg/kg body weight. Significantly different changes from the control group were observed in the 1,000 mg/kg group. The 1,000 mg/kg group showed elevations in renal NADP and NADPH contents and decrements in renal GSH content in the period of the 1st to 3rd hour after the CER-administration. Thus, the fall in renal GSH content was considered to be a cause for renal injury due to the oxygen radicals observed in the early period. After the 6th hour, the 1,000 mg/kg group showed decreases of renal glutathione peroxidase and glutathione reductase activities and increases of renal glucose-6-phosphate dehydrogenase activity as well as GSH content. Although accumulation of GSH in the kidney was clearly observed in the late period, the more highly aggravated renal injury was speculated to be due to the decreased level in the utilization of GSH according to the fall of renal glutathione peroxidase activity.