Potentiation of acute chloroform nephrotoxicity by the glutathione depletor diethyl maleate and protection by the microsomal enzyme inhibitor piperonyl butoxide

Abstract

Administration of chloroform (CHCl 3) to adult, male, ICR mice produced dose-dependent nephrotoxicity and hepatotoxicity. Prior administration of the glutathione-depleting agent diethyl maleate increased the susceptibility of the kidney to CHCl 3 injury, while prior administration of the microsomal enzyme inhibitor piperonyl butoxide reduced susceptibility to acute CHCl 3 injury. Piperonyl butoxide pretreatment did not alter the time sequence or the pathophysiological manifestations of acute CHCl 3 nephrotoxicity and hepatotoxicity. Treatment with piperonyl butoxide 1 hr after CHCl 3 exposure and treatment with the microsomal enzyme inhibior SKF 525-A 2 hr before or 1 hr after CHCl 3 failed to reduce the susceptibilities of the kidney and liver to acute CHCl 3 injury and, in fact, generally increased susceptibility to CHCl 3. These results suggest that renal glutathione may protect the kidney from acute CHCl 3 injury and indicate that CHCl 3 may be metabolized to a nephrotoxicant by an enzymatic pathway inhibited by piperonyl butoxide, but not by SKF 525-A.