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Modulation of UDPGlucuronosyltransferase Activity in Rats by Dietary Lipids¹

Laboratoire de Biochimie Pharmaceutique associé au PIREN n° 8287, Faculté des Sciences Pharmaceutiques et Biologiques, 7, Boulevard Jeanne d'Arc, 21000 Dijon ^* Laboratoire de Biochimie Pharmacologique, Unité Associée au C. N. R. S. n° 597, Centre du Médicament, 30, rue Lionnois, 54000 Nancy, France

Male Wistar rats were fed for 40 d a purified diet whose lipid source (60 g/kg diet) was coconut, peanut, corn or fish (herring) oil. A low lipid (lipid-deficient) diet (corn oil, 2 g/kg diet) was also fed to some rats. There were no significant differences in final body weights of rats fed the coconut, peanut, and corn oil diets. Rats fed the fish oil diet gained less weight than those fed any other diet. However, liver weight, ratio of liver to body weight, and protein content were not affected by any of the diets. The plasma cholesterol concentration of rats fed fish oil was lower than that of the other groups of rats. This diet resulted in the highest cytochrome P-450 concentration and markedly enhanced epoxide hydrolase activity. No difference in the level in cytochrome P-450 was noted between the groups of rats fed the vegetable oils. Epoxide hydrolase activity was also significantly higher with the corn oil diet. Interestingly, only glucuronidation of group I substrates was stimulated by the fish or corn oil diets and lowered by the coconut oil diet. Liver microsomes of rats fed fish oil contained a high level of lipid peroxides; this diet greatly stimulated NADPH-dependent peroxidation. The differential stimulation of UDPglucuronosyltransferase activity towards group I substrates could be the results of a toxic action of the fish oil diet as suggested by the concomitant enhancements of epoxide hydrolase, transaminase activities and peroxide content.

KEY WORDS: • dietary lipids • UDPglucuronosyltransferases • cytochrome P-450 • epoxide hydrolase • lipid peroxides

¹ This work was supported, in part, by the Fondation pour la Recherche Médicale, France.

² Address reprint request to Dr. J. Magdalou.

Manuscript received 19 February 1985. Revision accepted 15 May 1986.