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Masuda Y, Nakayama N: Protective action of diethyldithiocarbamate and carbon disulfide against renal injury induced by chloroform in mice. Biochem Pharmacol. 1983 Nov 1;32(21):3127-35. Oral administration of diethyldithiocarbamate (DTC) and carbon disulfide (CS2) protected mice against CHCl3-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 CCl4-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 CHCl3 was greatly potentiated, and the latter effect was also blocked by both agents. DTC and CS2 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 CCl4-treated mice. The protection was not due to hypothermia, because pretreatment with DTC or CS2 (p.o.) also prevented the hypothermia induced by CHCl3. The mechanism of the protection may have involved inhibition of metabolic activation of CHCl3 in the kidney rather than in the liver. |
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