Oral nitrite ameliorates dextran sulfate sodium-induced acute experimental colitis in mice |
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Authors: | Kazuo Ohtake Midori Koga Hiroyuki Uchida Kunihiro Sonoda Junta Ito Masaki Uchida Hideshi Natsume Jun Kobayashi |
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Institution: | 1. Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan;2. Department of Food and Nutritional Environment, College of Human Life and Environment, Kinjo Gakuin University, Nagoya, Japan;3. Division of Pharmaceutics, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan |
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Abstract: | Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of the intestinal tract with excessive production of cytokines, adhesion molecules, and reactive oxygen species. Although nitric oxide (NO) is reported to be involved in the onset and progression of IBDs, it remains controversial as to whether NO is toxic or protective in experimental colitis. We investigated the effects of oral nitrite as a NO donor on dextran sulfate sodium (DSS)-induced acute colitis in mice. Mice were fed DSS in their drinking water with or without nitrite for up to 7 days. The severity of colitis was assessed by disease activity index (DAI) observed over the experimental period, as well as by the other parameters, including colon lengths, hematocrit levels, and histological scores at day 7. DSS treatment induced severe colitis by day 7 with exacerbation in DAI and histological scores. We first observed a significant decrease in colonic nitrite levels and increase in colonic TNF-α expression at day 3 after DSS treatment, followed by increased colonic myeloperoxidase (MPO) activity and increased colonic expressions of both inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) at day 7. Oral nitrite supplementation to colitis mice reversed colonic nitrite levels and TNF-α expression to that of normal control mice at day 3, resulting in the reduction of MPO activity as well as iNOS and HO-1 expressions in colonic tissues with clinical and histological improvements at day 7. These results suggest that oral nitrite inhibits inflammatory process of DSS-induced experimental colitis by supplying nitrite-derived NO instead of impaired colonic NOS activity. |
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