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Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2007 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, Vol. 42, no 4, 510-518 p.Article in journal (Refereed) Published
Abstract [en]

Nitrate is abundant in our diet with particularly high levels in many vegetables. Ingested nitrate is concentrated in saliva and reduced to nitrite by bacteria in the oral cavity. We recently reported that application of nitrite-containing saliva to the gastric mucosa increases superficial blood flow and mucus generation via acid-catalyzed formation of bioactive nitrogen oxides including nitric oxide. Here we studied if dietary supplementation with nitrate would protect against gastric damage caused by a nonsteroidal anti-inflammatory drug. Rats received sodium nitrate in the drinking water for 1 week in daily doses of 0.1 or 1 mmol kg− 1. Control rats received 1 mmol kg− 1 sodium chloride. Diclofenac (30 mg kg− 1) was then given orally and the animals were examined 4 h later. In separate experiments we studied the effects of dietary nitrate on intragastric NO levels and mucus formation. Luminal levels of NO gas were greatly increased in nitrate-fed animals. The thickness of the mucus layer increased after nitrate supplementation and gene expression of MUC6 was upregulated in the gastric mucosa. Nitrate pretreatment dose dependently and potently reduced diclofenac-induced gastric lesions. Inflammatory activity was reduced in the rats receiving nitrate as indicated by lower mucosal myeloperoxidase activity and expression of inducible NO synthase. We conclude that dietary nitrate protects against diclofenac-induced gastric ulcers likely via enhanced nitrite-dependent intragastric NO formation and concomitant stimulation of mucus formation. Future studies will reveal if a diet rich in nitrate can offer an additional nutritional approach to preventing and treating peptic ulcer disease.

Place, publisher, year, edition, pages
2007. Vol. 42, no 4, 510-518 p.
Keyword [en]
Animals, Anti-Inflammatory Agents; Non-Steroidal/*adverse effects, Base Sequence, DNA Primers, Diclofenac/*adverse effects, Diet, Gastric Mucosa/metabolism, Male, Mucins/genetics, Nitrates/*administration & dosage, Nitric Oxide/metabolism, Rats, Rats; Sprague-Dawley, Stomach Ulcer/chemically induced/*prevention & control
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-13072DOI: 10.1016/j.freeradbiomed.2006.11.018PubMedID: 17275683OAI: oai:DiVA.org:uu-13072DiVA: diva2:40842
Available from: 2008-01-21 Created: 2008-01-21 Last updated: 2010-04-06Bibliographically approved

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Petersson, JoelPhillipson, MiaHolm, Lena
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