Comparative induction of drug-metabolizing enzymes by hypolipidaemic compounds

1. The inducing effect of hypolipidaemic compounds containing arylcarboxylic structure (fenofibrate, bezafibrate, ciprofibrate) on drug-metabolizing enzymes was compared with that of other chemically different molecules (probucol, 1-benzylimidazole) in rat liver. 2. Hepatomegaly was closely associated to the decrease in triglycerides and cholesterol contents in plasma. 3. Lauric acid hydroxylation and hydratation of trans-stilbene oxide by the cytosolic epoxide hydrolase were markedly increased by the arylcarboxylic acids (fenofibrate, bezafibrate and ciprofibrate). The determination of the concentration in microsomal epoxide hydrolase by immunoassay revealed no change in the protein amount within the membrane; only the specific activity was enhanced by bezafibrate and 1-benzylimidazole, suggesting an activation process. 4. Bilirubin glucuronidation was increased by the arylcarboxylic structures and by 1-benzylimidazole; by contrast probucol decreased this activity.