Influence of alcohol, dithiocarb and (+)-catechin on the hepatotoxicity and metabolism of vinylidene chloride in rats.
Hepatotoxicity of vinylidene chloride (1, 1-dichloroethylene, VDC) in rats was evidenced by increases of serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH). Simultaneous treatment with ethanol (4.8 g kg-1; p.o.) totally inhibited these hepatotoxic effects, whereas pretreatment with the same ethanol dose 24 h prior to VDC had no effect. Dithiocarb or (+)-catechin (0.2 g kg-1; p.o.), administered simultaneously with VDC, significantly reduced the VDC-induced increments of serum enzyme activities. Pretreatment with 5% ethanol for 7 days instead of drinking water increased the hepatotoxicity of a single dose of VDC. The combined treatment with VDC (0.125-0.2 g kg-1, twice weekly) and 5% ethanol for 4 weeks led to only small increases of serum enzyme activities as compared with controls treated with VDC alone. However, 60% lethality occurred in the VDC-ethanol group. Administration of either dithiocarb or (+)-catechin with VDC totally antagonized the observed lethality. Metabolic studies with VDC in a closed exposure system indicated that simultaneous treatment with ethanol or dithiocarb totally depressed the metabolic removal of VDC, whereas (+)-catechin had no effect.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D004050:Ditiocarb / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013859:Thiocarbamates / Q000494:pharmacology*; D014867:Water / Q000008:administration & dosage
D001578:Benzopyrans; D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D013859:Thiocarbamates; D014867:Water; D000431:Ethanol; D002392:Catechin; D004050:Ditiocarb