The effects of diethyldithiocarbamate and carbon disulfide on acute nephrotoxicity induced by furan, bromobenzene and cephaloridine in mice.
In previous studies (Masuda and Nakayama, 1983), diethyldithiocarbamate (DTC) and carbon disulfide (CS2) have been found to be protective against acute nephrotoxicity induced by CHCl3 and 1,1-dichloroethylene in normal and CCl4-poisoned mice, and it has been suggested that the protective action of DTC and CS2 might be mediated through inhibition of bioactivation of these nephrotoxicants in the kidney. As an extension of these studies, similar experiments were undertaken with furan, bromobenzene and cephaloridine, other nephrotoxic agents that are also thought to require metabolic activation. DTC or CS2 prevented mice from suffering renal injury induced by furan and bromobenzene, as evidenced by suppression of elevations in plasma urea nitrogen concentration and kidney calcium content and of morphologic alterations. Cephaloridine nephrotoxicity, however, was not prevented. In CCl4-poisoned mice, furan nephrotoxicity was augmented, whereas bromobenzene and cephaloridine nephrotoxicity was suppressed. The augumented furan nephrotoxicity was also prevented by DTC or CS2. These observations suggest that furan, like CHCl3 and 1,1-dichloroethylene, may exert nephrotoxicity through active metabolites formed in the kidney. For bromobenzene and cephaloridine nephrotoxicity, a renal bioactivation mechanism is suspected. DTC and CS2 also protected against hepatotoxicity induced by furan and thiophene.
D000818:Animals; D001969:Bromobenzenes; D002246:Carbon Disulfide / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology; D002509:Cephaloridine / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology*; D005663:Furans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013859:Thiocarbamates / Q000494:pharmacology*
D001969:Bromobenzenes; D005663:Furans; D013859:Thiocarbamates; D004050:Ditiocarb; D002509:Cephaloridine; D002246:Carbon Disulfide