Changes in drug-metabolizing enzymes of rats in ciprofibrate-induced hepatic nodules.
1. Premalignant rat liver nodules produced in the resistant hepatocyte model, by exposure to carcinogenic chemicals (diethyl nitrosamine and 2-acetamidofluorene), and partial hepatectomy, exhibit decreased xenobiotic hydroxylase activities and increased conjugase activities, which are considered responsible for increased resistance to xenobiotic toxicity. 2. However, premalignant rat liver nodules generated by feeding the hypolipidaemic, peroxisomal proliferating drug, ciprofibrate, in a hypolipidaemic model, exhibit decreased hydroxylase activities but decreased conjugase activities also. 3. It is considered that reactive oxygen species (ROS) are generated in both the resistant hepatocyte model and in the hypolipidaemic model, resulting in lipid peroxidation, loss of haem, cytochromes and hydroxylase activities. 4. However, whereas there is a rebounding compensation of conjugase enzymes in the resistant hepatocyte model, this does not occur with the hypolipidaemic model, as peroxidation is probably persistent and the conjugases are continuously destroyed.
Roomi
M W
MW
Department of Pathology, University of Toronto, Canada.
Farber
E
E
Parke
D V
DV
D015073:2-Acetylaminofluorene; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D002273:Carcinogens; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D003043:Cocarcinogenesis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004052:Diethylnitrosamine; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000097:blood; D058607:Fibric Acids; D006498:Hepatectomy; D000960:Hypolipidemic Agents / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D002273:Carcinogens; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D017382:Reactive Oxygen Species; D004052:Diethylnitrosamine; D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D000633:Aminopyrine N-Demethylase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C059607:glycylprolyl dipeptidase; C019304:ciprofibrate