Protective action of diethyldithiocarbamate and carbon disulfide against renal injury induced by chloroform in mice

Abstract

Oral administration of diethyldithiocarbamate (DTC) and carbon disulfide (CS 2) protected mice against CHCl 3-induced kidney injury, as evidenced by normalization of delayed plasma phenolsulfonphthalein clearance, suppression of increased kidney calcium content and prevention of renal tubular necrosis. In CCl 4-treated mice, in which liver microsomal monooxygenase activities were decreased markedly, and kidney microsomal aniline hydroxylase and p-nitroanisole demethylase activities were increased to about twice those of the untreated mice, renal toxicity of CHCl 3 was greatly potentiated, and the latter effect was also blocked by both agents. DTC and CS 2 per se markedly decreased kidney microsomal aniline hydroxylase and p-nitroanisole demethylase activities at 1 hr after oral administration, accompanying a moderate loss of cytochrome P-450 content, in both normal and CCl 4-treated mice. The protection was not due to hypothermia, because pretreatment with DTC or CS 2 (p.o.) also prevented the hypothermia induced by CHCl 3. The mechanism of the protection may have involved inhibition of metabolic activation of CHCl 3 in the kidney rather than in the liver.