Hepatic epoxide hydrolase activities and their induction by clofibrate and diethylhexylphthalate in various strains of mice

Abstract

The presence of epoxide hydrolase activity in cytoplasm, microsomes and mitochondrial fraction in livers from twelve strains of mice (AKR/J, A/J, BALB/cByJ, CBA/J, C3H/HeJ, G57BL/6J, C57BL/10J, DBA/2J, NZB/B1NJ, PL/J, SEC/1ReJ and SW), and the influence of orally administered clofibrate and di(2-ethylhexyl)phthalate (DEHP) (0.5 and 2%, respectively, in diet) on epoxide hydrolase activities, were studied. Significant differences in basal cytosolic epoxide hydrolase activity, which ranged from 5.6 to 11.2 nmol diol · min −1 · (mg protein) −1 using trans-stilbene oxide (TSO) as substrate, were noted among the mice. The highest and lowest enzyme levels were observed in the A/J and DBA/ 2J strains respectively. Similarly, microsomal epoxide hydrolase activity, monitored with cis-stilbene oxide (CSO), varied with the mouse strain, with the highest and lowest microsomal epoxide hydrolase activity being observed in A/J and SW strains respectively. Variations were also noted in the epoxide hydrolase activity in the mitochondrial fraction (monitored with TSO) with the highest and lowest levels observed in C57BL/6J and SW strains respectively. Clofibrate or DEHP treatment induced both cytosolic and microsomal epoxide hydrolases in nearly all of the strains examined. In contrast, the hydrolysis of TSO by the mitochondrial fraction in these strains was either not affected or decreased by clofibrate or DEHP treatment. The induction of cytosolic epoxide hydrolase was found to range between 1.2- and 2.8-fold, with generally a higher level of induction in mouse strains with low basal levels of cytosolic epoxide hydrolase activity. This level of cytosolic epoxide hydrolase activity, monitored with TSO as substrate, closely reflected the level of cytosolic epoxide hydrolase protein detected by immunoblot. There were also no significant differences observed in the molecular weight, immunological characteristics, pH-dependence and heat stability of hepatic cytosolic epoxide hydrolase activities of control and clofibrate-treated mice from various strains. These results suggest that clofibrate and DEHP induce both cytosolic and microsomal epoxide hydrolases but not the epoxide hydrolase in the mitochondrial fraction.