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J.Health Sci., 49(2), 105-114, 2003

The Effect of Dietary Fatty Acids on the Expression Levels and Activities of Hepatic Drug Metabolizing Enzymes

Junko Kato, Atsushi Ikemoto, and Takaharu Mizutani*

Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

Analysis of the fatty acid composition in the microsomes of rats fed the oil rich in alpha-linolenic acid (n-3, perilla oil, Per) or linoleic acid (n-6, safflower oil, Saf) showed changes according to those compositions in the diets. The level of phase I enzyme in microsomes prepared from rat liver was measured by the Western blotting method. The levels of CYP1A1, 1A2 and 2E1 were similar between the two oil groups, Per and Saf. Meanwhile, the level of CYP4A1 in the microsomes of rats fed the Per diet was significantly higher than that from rats fed Saf. As a second step, we measured the level and activity of UDP-glucuronosyltransferase (UGT). The results showed that the level of UGT activity in microsomes from rats fed the Per diet was 2.4-fold higher than that from rats fed the Saf diet. The protein level of UGT in microsomes from rats fed the Per diet was also 1.7-fold greater than that from rats fed the Saf diet. The low level of protein amount and activity of UGT in rats fed Saf was recovered by the administration of the Per diet. Furthermore, the UGT activity in microsomes from rats fed high docosahexaenoic acid, another n-3 fatty acid, was higher than that in rats fed Per oil. These results suggest that the fatty acid composition, n-3 or n-6, in foods influences the level and activity of CYP4A and UGT. Thus, monitoring of the drug level in the blood of patients in consideration of oil intake should be undertaken.