EFFECTS OF ENTERAL NUTRITION AND ETHANOL ON CYTOCHROME-P450 DISTRIBUTION IN SMALL-INTESTINE OF MALE-RATS

Background: Alcohol and nutrition are important factors regulating hepatic cytochrome P450 isozymes. The current studies were conducted to determine if intestinal P450 isozymes were similarly regulated. Methods: Adult male Sprague-Dawley rats were infused intragastrically with control or ethanol-containing diets. Western blot analysis was used to study CYP1A, CYP2B, and CYP3A isozymes in microsomes of three regions of the small intestine and liver. Results: Compared with rats eating standard rat food, rats receiving the total enteral nutrition diet had reduced expression of several P450 isozymes in the intestine, especially in the jejunal region. Two CYP1A forms were detected by Western blot analysis in the small intestine with electrophoretic mobilities corresponding to hepatic CYP1A1 and CYP1A2. These forms appeared to be differentially regulated. Long-term ethanol treatment resulted in reduction of CYP3A and CYP1A apoprotein levels in the jejunal region. Conclusions: The P450 isozymes examined displayed differing intestinal distributions, responded to dietary manipulations, and were affected by ethanol treatment in a fashion not coordinated with that observed for hepatic isozymes. © 1993.