Protective action of diethyldithiocarbamate and carbon disulfide against various nephrotoxic agents.

Abstract

Diethyldithiocarbamate (DTC) and carbon disulfide (CS2) protected mice against nephrotoxicity induced by chloroform, 1,1-dichloroethylene (1,1-DCE), furan, bromobenzene but not cephaloridine. Nephrotoxicity of chloroform and 1,1-DCE, but not that of furan, was augmented in CCl4-poisoned mice, which was also protected by DTC and CS2. Bromobenzene nephrotoxicity was, however, suppressed in CCl4-poisoned mice. CCl4-poisoning produced a marked decrease in liver microsomal monooxygenase (MO) activities and cytochrome P-450 content, whereas some renal microsomal MO activities such as aniline hydroxylase and p-nitroanisole O-demethylase were rather increased. DTC and equimolar doses of CS2 reduced these renal microsomal MO activities and cytochrome P-450 content in both normal and CCl4-poisoned mice. Thus, nephrotoxicity of chloroform, 1,1-DCE and furan may result from metabolic activation of these nephrotoxins in the kidney MO system. Bromobenzene nephrotoxicity, however, may be evoked by active metabolites formed in the liver and transferred to the kidney. Renal microsomal bioactivation may not be required in the case of cephaloridine nephrotoxicity. The action of DTC, especially when given orally, may be mediated through CS2 produced in the stomach, which probably inhibits metabolic activation of some nephrotoxins in the kidney.