Role of liver glutathione in 1,1-dichloroethylene metabolism and hepatotoxicity in intact rats and isolated perfused rat liver.
The liver glutathione content was measured after oral administration of 1,1-dichloroethylene (vinylidene chloride = VDC; dissolved in olive oil) and its significance for the metabolism and hepatotoxicity of VDC was investigated. After treatment with 1000 mg/kg VDC p.o., glutathione decreased to 33% of the control values within 4 h but returned to the control level after 24 h. An identical fall in glutathione after VDC administration was found to occur in animals which had been fasted for 18 h. In these animals the baseline values of glutathione were lowered by 21%. The depletion of glutathione was dependent on the dosage of VDC. The conversion rate of VDC by the isolated perfused livers was 7.64 mumoles/g liver after 3 h-perfusion, if 5000 ppm of VDC were supplied in the gas phase. Lowering the glutathione content to 15% of the normal value (by diethylmaleate, 25 mumoles added directly to the perfusate) resulted in a reduction of VDC conversion by 18%. Furthermore the viability (with the lactate/pyruvate ratio serving as the parameter) of the liver was distinctly depresesd. No effect on viability nor on metabolization rate was noted when perfusing the livers of 18-h fasted animals. The concentrations of the glutamate-oxaloacetate transaminase (SGOT) and glutamate-pyruvate transaminase (SGPT) in the perfusate failed to show an increase. These findings indicate that there is no correlation between the liver glutathione level and the increased lethality of VDC in fasted rats.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004000:Dichloroethylenes / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D005978:Glutathione