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.