Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease.

Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease.
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DOI:
10.1016/j.redox.2013.12.012
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发表时间:
2014
期刊:
影响因子:
11.4
通讯作者:
Borniquel, Sara
Borniquel, Sara
中科院分区:
生物学1区
文献类型:
--
作者:
Jadert, Cecilia;Phillipson, Mia;Holm, Lena;Lundberg, Jono O.;Borniquel, Sara

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Inorganic nitrate and nitrite have emerged as alternative substrates for nitric oxide (NO) generation in the gastrointestinal tract, and have shown to be protective against drug-induced gastric injury. The aim of this study was to investigate the preventive and therapeutic effects of nitrate and nitrite in a model of experimental colitis. Colitis was induced in mice by administrating dextran sulfate sodium (DSS) with concurrent administration of nitrite (1 mM) or nitrate (10 mM) in the drinking water for 7 days. A therapeutic approach was also investigated by initiating nitrite treatment 3 days after DSS-induced colitis. Clinical and inflammatory markers were assessed and the colonic mucus thickness was measured in vivo. The effect of nitrite on wound healing was evaluated using colon epithelial cells. Concurrent administration of DSS and nitrite (1 mM) alleviated inflammation as determined by reduced disease activity index score (DAI) and increased colon length, while nitrate (10 mM) only reduced the DAI-score. Nitrite also displayed therapeutic effects by ameliorating established colonic inflammation with reduced colonic expression of iNOS and improving histopathology. DSS-induced decrease in colonic mucus thickness was completely prevented by nitrite administration. In addition, goblet cell abundance was lower by DSS treatment, but was increased by addition of nitrite. Further studies using colon epithelial cells revealed an NO-dependent improvement in wound healing with nitrite administration. Nitrite exerts both preventive and therapeutic effects in colonic inflammation. The protective effects involve preservation of an intact adherent mucus layer and regulation of epithelial cell restitution. Inorganic nitrate and nitrite alleviate DSS-induced colitis. Dietary nitrite has therapeutic effects in already established colonic inflammation. DSS-induced thinning of the colonic mucus layer is prevented by dietary nitrite. Nitrite promotes healing of colon epithelial cells.
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