title: Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model.
abstract: The effect of rebamipide, a mucosal protective drug, on small intestinal mucosal injury caused by indomethacin was examined using a rat model. Indomethacin administration (10 mg/kg, p.o.) induced intestinal mucosal injury was accompanied by an increase in the numbers of intestinal bacteria particularly Enterobacteriaceae in the jejunum and ileum. Rebamipide (30 and 100 mg/kg, p.o., given 5 times) was shown to inhibit the indomethacin-induced small intestinal mucosal injury and decreased the number of Enterococcaceae and Enterobacteriaceae in the jejunal mucosa to normal levels. It was also shown that the detection rate of segmented filamentous bacteria was increased by rebamipide. PCR array analysis of genes related to inflammation, oxidative stress and wound healing showed that indomethacin induced upregulation and downregulation of 14 and 3 genes, respectively in the rat jejunal mucosa by more than 5-fold compared to that of normal rats. Rebamipide suppressed the upregulated gene expression of TNFα and Duox2 in a dose-dependent manner. In conclusion, our study confirmed that disturbance of intestinal microbiota plays a crucial role in indomethacin-induced small intestinal mucosal injury, and suggests that rebamipide could be used as prophylaxis against non-steroidal anti-inflammatory drugs -induced gastrointestinal mucosal injury, by modulating microbiota and suppressing mucosal inflammation in the small intestine.
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurata
authors.affiliation: Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Uematsu
authors.affiliation: Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shibamori
authors.affiliation: Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
keywords: intestinal flora; non-steroidal anti-inflammatory drugs; oxidative stress; rebamipide; small intestine
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