Protective action of diethyldithiocarbamate and carbon disulfide against acute toxicities induced by 1,1-dichloroethylene in mice.
In male mice of ddY strain, a single dose of 1,1-dichloroethylene (1,1-DCE, 0.1 ml/kg, ip) produced severe renal damage at 24 hr, as evidenced by elevations in plasma urea nitrogen concentration and kidney calcium content and by massive renal tubular necrosis, while hepatic damage was less severe. A precipitous decrease in body temperature started as early as 30 min after administration of 1,1-DCE and lasted for 24 hr. Glutathione concentrations decreased in the liver and kidney, with a rebound increase seen in the former but not in the latter tissue. In carbon tetrachloride-poisoned mice, the renal toxicity of 1,1-DCE was markedly potentiated. Pretreatment with either diethyldithiocarbamate (DTC) or carbon disulfide (CS2) blocked all of these 1,1-DCE-induced toxic manifestations in normal and carbon tetrachloride-poisoned mice. Both agents, however, did not prevent the hypothermia induced by monochloroacetic acid or chloroacetyl chloride, proposed active metabolites of 1,1-DCE. Since DTC and CS2 inhibited hepatic and renal microsomal drug metabolizing enzyme activities (Masuda and Nakayama, 1982, 1983), it is probable that the protective action of DTC and CS2 against renal and hepatic injury induced by 1,1-DCE may be due to an inhibition of the metabolic activation of 1,1-DCE to its proposed epoxide in each organ. The action of DTC given po may be mediated by CS2 produced in the stomach. The hypothermia induced by 1,1-DCE may not result from a direct action of 1,1-DCE per se, but by its metabolites.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002246:Carbon Disulfide / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004050:Ditiocarb / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013859:Thiocarbamates / Q000494:pharmacology*
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D013859:Thiocarbamates; D004050:Ditiocarb; D002251:Carbon Tetrachloride; D005978:Glutathione; D002246:Carbon Disulfide