Interactions among nephrotoxicants: N-(3,5-dichlorophenyl)succinimide and cephaloridine

Numerous studies have demonstrated the interactive potential between nephrotoxicants. The purpose of this study was to examine the interactive potential between two model nephrotoxicants, N-(3,5-dichlorophenyl)succinimide (NDPS) and cephaloridine (CPH). Male Fischer 344 rats (4 rats per group) were administered an intraperitoneal (i.p.) injection of CPH (500 mg/kg), NDPS (0.2 mmol/kg) or the appropriate vehicle 1 h prior to administration of an i.p. injection of NDPS (0.2, 0.4, or 1.0 mmol/kg), CPH (500, 750 or 1000 mg/kg) or the appropriate vehicle. Renal function was monitored at 24 and 48 h. Combination of non-nephrotoxic doses of CPH (500 mg/kg) and NDPS (0.2 mmol/kg) did not result in nephrotoxicity, regardless of which compound was administered first. NDPS (0.2 mmol/kg) weakly enhanced the nephrotoxicity observed following CPH (1000 mg/kg) injection but had little effect on CPH (750 mg/kg)-induced renal effects. However, CPH (500 mg/kg) markedly attenuated NDPS (0.4 or 1.0 mmol/kg)-induced nephrotoxicity. These results demonstrate that prior NDPS exposure has little effect on the outcome of CPH-induced renal effects, but prior CPH exposure can markedly alter the renal response to NDPS administration.