Effects of dithiocarb and (+)-cyanidanol-3 on the hepatotoxicity and metabolism of vinylidene chloride in rats.
The acute hepatotoxic effects of vinylidene chloride (VDC) were evidenced by measurement of the increase in the serum levels of the aminotransferase (GPT) and sorbitol dehydrogenase (SDH), hepatic glutathione (GSH) depletion and histological examinations in rats. The hepatoprotective agents dithiocarb and (+)-cyanidanol-3 proved well able to antagonize these toxic effects of VDC. While dithiocarb inhibited the in vivo metabolism of VDC in a closed exposure system, (+)-cyanidanol-3 had no influence at all. These findings substantiate the role of the microsomal monooxygenase system in the metabolism and hepatotoxicity of VDC. The mechanisms by which dithiocarb and (+)-cyanidanol-3 act as antihepatotoxic agents are different: the inhibition of the metabolic activation by dithiocarb and free radical-scavenging by (+)-cyanidanol-3.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology*; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004050:Ditiocarb / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007064:L-Iditol 2-Dehydrogenase / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology*; D000637:Transaminases / Q000032:analysis
D001578:Benzopyrans; D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D013859:Thiocarbamates; D002392:Catechin; D004050:Ditiocarb; D007064:L-Iditol 2-Dehydrogenase; D000637:Transaminases; D005978:Glutathione