Changes in drug-metabolizing enzymes of rats in ciprofibrate-induced hepatic nodules.

Xenobiotica 1997 Sep;27(9):951-60    

Roomi MW; Farber E ; Parke DV
Department of Pathology, University of Toronto, Canada.

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.