{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:03:36Z","timestamp":1791846216399,"version":"4.3.4"},"reference-count":182,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:p>Throughout the human gastrointestinal tract a variety of reactive nitrogen oxides are continuously formed as a result of a complex interplay between the host, commensal bacteria and dietary factors. These compounds include nitric oxide, nitrite, nitrate, peroxynitrite, S-nitrosothiols, nitrated fatty acids and N-nitrosamines, all of which are bioactive with the potential to affect physiological and pathological processes locally in the gut as well as systemically after absorption. Historically, the literature has been dominated by studies on the formation of potentially carcinogenic nitrosamines, but the focus was shifted in the 1980s with the seminal discovery of the L-arginine-nitric oxide pathway and its profound impact on normal physiological functions. More recently, a nitrate-nitrite-nitric oxide pathway has been discovered, with implications for local host defence and gut mucosal integrity and, intriguingly, also for systemic regulation of cardiovascular and metabolic function. This review discusses recent advances in the understanding of the formation, biochemistry, physiology and pathophysiology of reactive nitrogen oxides in the gastrointestinal tract. In addition, opportunities for nitric oxide-based pharmacological or dietary interventions are highlighted.<\/jats:p>","DOI":"10.1136\/gutjnl-2011-301649","type":"journal-article","created":{"date-parts":[[2012,1,21]],"date-time":"2012-01-21T01:42:39Z","timestamp":1327110159000},"page":"616-629","source":"Crossref","is-referenced-by-count":165,"title":["Biology of nitrogen oxides in the gastrointestinal tract"],"prefix":"10.1136","volume":"62","author":[{"given":"Jon O","family":"Lundberg","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Weitzberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2012,1,20]]},"reference":[{"key":"2025121223312588000_62.4.616.1","doi-asserted-by":"publisher","DOI":"10.2165\/00139709-200322010-00005"},{"key":"2025121223312588000_62.4.616.2","doi-asserted-by":"publisher","DOI":"10.2307\/3432236"},{"key":"2025121223312588000_62.4.616.3","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/317675b0","article-title":"Nitrate and gastric cancer risks","volume":"317","author":"Tannenbaum","year":"1985","journal-title":"Nature"},{"key":"2025121223312588000_62.4.616.4","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(95)03786-V"},{"key":"2025121223312588000_62.4.616.5","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(88)90194-7"},{"key":"2025121223312588000_62.4.616.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312303292706"},{"key":"2025121223312588000_62.4.616.7","first-page":"503","article-title":"Nitric oxide as a unique signaling molecule in the vascular system: a historical overview","volume":"53","author":"Ignarro","year":"2002","journal-title":"J Physiol Pharmacol"},{"key":"2025121223312588000_62.4.616.8","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"2025121223312588000_62.4.616.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.22.7738"},{"key":"2025121223312588000_62.4.616.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.6451927"},{"key":"2025121223312588000_62.4.616.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.2432665"},{"key":"2025121223312588000_62.4.616.12","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0031-6997(25)06663-3","article-title":"Nitric oxide: physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada","year":"1991","journal-title":"Pharmacol Rev"},{"key":"2025121223312588000_62.4.616.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00495-0"},{"key":"2025121223312588000_62.4.616.14","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2466"},{"key":"2025121223312588000_62.4.616.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro929"},{"key":"2025121223312588000_62.4.616.16","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.260"},{"key":"2025121223312588000_62.4.616.17","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1080\/15287397709529529","article-title":"N-nitroso compounds: their chemical and in vivo formation and possible importance as environmental carcinogens","volume":"2","author":"Mirvish","year":"1977","journal-title":"J Toxicol Environ Health"},{"key":"2025121223312588000_62.4.616.18","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1956.15"},{"key":"2025121223312588000_62.4.616.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-6264(76)80005-3"},{"key":"2025121223312588000_62.4.616.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.451551"},{"key":"2025121223312588000_62.4.616.21","doi-asserted-by":"publisher","DOI":"10.1126\/science.7403871"},{"key":"2025121223312588000_62.4.616.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-6264(76)80006-5"},{"key":"2025121223312588000_62.4.616.23","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/8.12.1907"},{"key":"2025121223312588000_62.4.616.24","first-page":"292","article-title":"Endogenous formation of N-nitroso compounds: a current perspective","volume":"84","author":"Tannenbaum","year":"1987","journal-title":"IARC Sci Publ"},{"key":"2025121223312588000_62.4.616.25","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S0140-6736(76)90962-4","article-title":"Gastric-juice nitrite. 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