title: Interrelationship between in vivo lipid peroxidation, microsomal Ca2+-sequestration activity and hepatotoxicity in rats treated with carbon tetrachloride, cumene hydroperoxide or thioacetamide.
abstract: To study the relationship between lipid peroxidation and cellular damage we studied three compounds known to evoke lipid peroxidation (cumene hydroperoxide, CHP), hepatocellular injury (thioacetamide, TAA) or both (carbon tetrachloride, CCl4). Phenobarbital-induced male rats were treated with one of the three agents and lipid peroxidation was monitored via the measurement of exhaled ethane. Treatment with both, CCl4 and CHP resulted in an increased ethane expiration, whereas TAA did not. When liver-specific serum enzyme activities (GPT, SDH) were investigated 24 h later, however, hepatotoxicity was evident only in rats treated with either CCl4 or TAA. The ATP-dependent Ca2+-sequestration activity of microsomal membranes, suggested to be a final common pathway leading to cellular death, was studied in microsomes isolated from rats treated with either agent. 2 h after treatment with CCl4 or TAA a clear inhibition was seen which persisted after 24 h in the case of CCl4 only. CHP did not affect the Ca2- -pump activity. Thus, a clear correlation between cellular damage and lipid peroxidation cannot be expected in every case. An impairment of the microsomal calcium-pump, however, seems to be a crucial event which leads to hepatocellular injury.
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000633:toxicity; D013997:Time Factors
chemical_list: D001555:Benzene Derivatives; D008054:Lipid Peroxides; D013853:Thioacetamide; C007164:cumene hydroperoxide; D002118:Calcium