CEPHALORIDINE NEPHROTOXICITY IN DIABETIC RATS - MODULATION BY INSULIN-TREATMENT

Previous studies have indicated that cephaloridine nephrotoxicity was reduced in diabetic rats. This study determined whether the reduction in toxicity was due to streptozotocin or the diabetic state. Male Fisc her-344 rats were injected intraperitoneally with 35 mg/kg streptozoto cin to induce diabetes. Insulin (5 U/day, subcutaneously) was begun wi thin 72 h and continued for 10 days. Toxicity was quantitated 48 h aft er injection of cephaloridine (1500 mg/kg, i.p.) in normoglycemic (NC) , diabetic (DC) and diabetic animals treated with insulin (DIC). Cepha loridine produced diuresis, glucosuria, proteinuria, elevated kidney w eight and decreased renal cortical slice accumulation of organic ions in the NC group. Cephaloridine toxicity was reduced in the DC group si nce kidney weight, BUN level and renal cortical slice accumulation of organic anions were similar between treated and control animals. Cepha loridine treatment of the DIC group was associated with increased BUN levels, proteinuria and diminished renal cortical slice accumulation o f organic cations. These results indicated that the diabetic state, an d not streptozotocin, reduced cephaloridine nephrotoxicity.