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 Fischer-344 rats were injected intraperitoneally with 35 mg/kg streptozotocin to induce diabetes. Insulin (5 U/day, subcutaneously) was begun within 72 h and continued for 10 days. Toxicity was quantitated 48 h after injection of cephaloridine (1500 mg/kg, i.p.) in normoglycemic (NC), diabetic (DC) and diabetic animals treated with insulin (DIC). Cephaloridine produced diuresis, glucosuria, proteinuria, elevated kidney weight and decreased renal cortical slice accumulation of organic ions in the NC group. Cephaloridine toxicity was reduced in the DC group since kidney weight, BUN level and renal cortical slice accumulation of organic anions were similar between treated and control animals. Cephaloridine treatment of the DIC group was associated with increased BUN levels, proteinuria and diminished renal cortical slice accumulation of organic cations. These results indicated that the diabetic state, and not streptozotocin, reduced cephaloridine nephrotoxicity.