The in vivo toxicity of CS2 to liver microsomes: binding of labelled CS2 and changes of the microsomal enzyme activities.
The binding of 35S and 14C labelled CS2 to liver microsomes was studied in control and phenobarbitone pretreated rats 3 and 6 hrs after an intraperitoneal injection. The level of hepatic cytochrome P-450, the activities of epoxide hydratase and UDP-glucuronosyltransferase were analyzed in the same animals. The binding of the sulphur label was considerably higher than that of carbon 3 hrs after the injection, the difference being less evident at 6 hrs.T he measurable P-450 declined after the CS2 injection. It was approximately 40% in the phenobarbitone pretreated rats and 60% in control rats of the values of animals which were not treated with CS2. CS2 did not affect microsomal epoxide hydratase activity, while it increased the measurable activity of UDP-glucuronosyltransferase. The increase was evident 3 hrs after the injection of CS2 in the phenobarbitone pretreated rats. It could also be detected in the control animals 6 hrs after the injection. The present data suggest that the change in the measureble P-450 results from the binding of the metabolite(s) of CS2 to the cytochrome, and its subsequent degradation. The increase in measurable UDP-glycuronosyltransferase activity results probably from the activated perturbation of the structure of microsomal membrane by the metabolites of CS2 in vivo.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002246:Carbon Disulfide / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases; D002246:Carbon Disulfide; D010634:Phenobarbital