Oral nitrite ameliorates dextran sulfate sodium-induced acute experimental colitis in mice

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 7days. 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-alpha 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-alpha 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.

Identification of Galectin-2–Mucin Interaction and Possible Formation of a High Molecular Weight Lattice

“…23,24) Large quantities of NO are known to be generated in the stomach by the non-enzymatic acid reduction of salivary nitrite, in addition to the NO generated enzymatically by NO synthase from L-arginine, and have been proposed to exert various physiological functions in the gastrointestinal tract [35][36][37][38] including as a barrier in the stomach. [39][40][41] Therefore, it is possible that the NO generated in the stomach Snitrosylates Gal-2 to sustain a stronger barrier through the crosslinking of mucins and to prevent the oxidative inactivation of Gal-2.…”

Sepiapterin Ameliorates Chemically Induced Murine Colitis and Azoxymethane-Induced Colon Cancer

“…A previous study demonstrated that dietary supplementation with nitrite ameliorated DSS-induced colitis, possibly by bypassing NOS activity and using an alternative mechanism of NO generation involving the reduction of nitrite (Lundberg and Weitzberg, 2009;Ohtake et al, 2010). Our study examined the effect of modulating BH4 levels by dietary pretreatment of animals with sepiapterin (SP), a metabolic precursor of BH4, thereby enhancing the NO-sGC-PKG pathway and abrogating DSS induction of colitis and CRC.…”

Therapeutic effects of four molecular-weight fractions of Kurozu against dextran sulfate sodium-induced experimental colitis

“…Indeed, Ohtake et al (10) reported that oral administration of nitrite ameliorated DSS-induced colitis. Moreover, to our knowledge, there is no report indicating that nitrite itself aggravates DSS-induced colitis.…”