Reduced hepatic drug-metabolising enzyme activities in spontaneously hyperlipidaemic rat as an animal model of hypercholesterolaemia

We investigated the activities of hepatic drug-metabolising enzymes and the serum levels of lipids and sex steroids in spontaneously hyperlipidaemic rats (HLR) as compared with those in Sprague-Dawley rats (SDR) of both sexes. The serum cholesterol levels was significantly higher in HLR than in SDR in both sexes. Serum testosterone and estradiol levels of HLR were significantly lower than those of SDR in males and females, respectively. The activities of arylhydroxycarbon hydroxylase (AHH), flavin-containing monooxygenase (FMO) and uridine diphosphate glucuronyl transferase (UDP-GT) of HLR were significantly lower than those of SDR in both sexes. HLR showed significantly lower activities of aniline hydroxylase, aminopyrine N-demethylase and glutathione S-transferase (GST) than SDR only in females. These results suggest that lower activities of hepatic drug-metabolising enzymes in HLR might be related to the significant increase in serum cholesterol, and/or significant decrease in sex steroids, as compared with those in SDR.