Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Elevated rates of generation of these oxidative inflammatory mediators can have direct effects on enterocytes and mucosal integrity, impair NO-dependent vascular function, reduce nitrate and nitrite absorption, and exert selective pressure on bacteria by augmenting innate anti-bacterial effects.
“Elevated rates of generation of these oxidative inflammatory mediators can have direct effects on enterocytes and mucosal integrity, impair NO-dependent vascular function, reduce nitrate and nitrite absorption, and exert selective pressure on bacteria by augmenting innate anti-bacterial effects[204,233,321–324].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [321]
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- Authors
- Jädert, C., Phillipson, M., Holm, L., Lundberg, J. O., & Borniquel, S.
- Affiliations
- Karolinska Institutet (SE)
- Uppsala University (SE)
- Corresponding author
- Borniquel, Sara
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 2
- Pages
- 73-81
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC3909265
- OpenAlex
- W1974814200
- Cited by
- 73
- References
- 65
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 11 · 2014: 3
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Karolinska Institutet
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- nitrite, nitrate, nitric oxide, inflammatory bowel disease, colitis, dextran sulfate, colonic mucus, goblet cells, epithelial repair, inducible nitric oxide synthase, colonic epithelial cells, preventive effect
- MeSH terms
- Animals, Cell Line, Colitis, Colon, Disease Models, Animal, Drug Administration Schedule, Female, Humans, Mice, Inbred BALB C, Nitrates, Nitrites, Wound Healing, Dextran Sulfate, Dietary Supplements, Mice
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