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However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin\u2010induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down\u2010regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor \u03b1, interleukin (IL)\u20101\u03b2 and IL\u20106, in the small intestine and the liver. The indomethacin\u2010induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down\u2010regulation of CYP3A1 expression in the liver were inhibited by co\u2010administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL\u20101\u03b2, IL\u20106 and NOC\u201018, an NO donor, caused down\u2010regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down\u2010regulation of CYP3A1 in the rat liver through an increase in ulcer\u2010derived inflammatory mediators. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.2042","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T11:17:17Z","timestamp":1474888637000},"page":"522-532","source":"Crossref","is-referenced-by-count":3,"title":["Down\u2010regulation of hepatic CYP3A1 expression in a rat model of indomethacin\u2010induced small intestinal ulcers"],"prefix":"10.1002","volume":"37","author":[{"given":"Shoji","family":"Kawauchi","sequence":"first","affiliation":[{"name":"Educational Center for Clinical Pharmacy Kobe Pharmaceutical University  4\u201019\u20101 Motoyamakitamachi, Higashinada\u2010ku Kobe 658\u20108558 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Education and Research Center for Clinical Pharmacy Osaka University of Pharmaceutical Sciences  4\u201020\u20101 Nasahara, Takatsuki Osaka 569\u20101094 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