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- Jansson, Emmelie A, et al.
(author)
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Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate
- 2007
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 42:4, s. 510-518
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Petersson, Joel, et al.
(author)
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Dietary nitrate increases gastric mucosal blood flow and mucosal defense
- 2007
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In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 292:3, s. G718-G724
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Journal article (peer-reviewed)abstract
- Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to bioactive nitrogen oxides, including nitric oxide (NO). In this study, we investigated the gastroprotective role of nitrate intake and of luminally applied nitrite against provocation with diclofenac and taurocholate. Mucosal permeability (51Cr-EDTA clearance) and gastric mucosal blood flow (laser-Doppler flowmetry) were measured in anesthetized rats, either pretreated with nitrate in the drinking water or given acidified nitrite luminally. Diclofenac was given intravenously and taurocholate luminally to challenge the gastric mucosa. Luminal NO content and nitrite content in the gastric mucus were determined by chemiluminescence. The effect of luminal administration of acidified nitrite on the mucosal blood flow was also investigated in endothelial nitric oxide synthase-deficient mice. Rats pretreated with nitrate or given nitrite luminally had higher gastric mucosal blood flow than controls. Permeability increased more during the provocation in the controls than in the nitrate- and nitrite-treated animals. Dietary nitrate increased luminal NO levels 50 times compared with controls. Nitrate intake also resulted in nitrite accumulation in the loosely adherent mucous layer; after removal of this mucous layer, blood flow was reduced. Nitrite administrated luminally in endothelial nitric oxide synthase-deficient mice increased mucosal blood flow. We conclude that dietary nitrate and direct luminal application of acidified nitrite decrease diclofenac- and taurocholate-induced mucosal damage. The gastroprotective effect likely involves a higher mucosal blood flow caused by nonenzymatic NO production. These data suggest an important physiological role of nitrate in the diet.
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| 3. |
- Petersson, Joel, et al.
(author)
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Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash
- 2009
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 46:8, s. 1068-1075
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Journal article (peer-reviewed)abstract
- Recently, it has been suggested that the supposedly inert nitrite anion is reduced in vivo to form bioactive nitric oxide with physiological and therapeutic implications in the gastrointestinal and cardiovascular systems. Intake of nitrate-rich food such as vegetables results in increased levels of circulating nitrite in a process suggested to involve nitrate-reducing bacteria in the oral cavity. Here we investigated the importance of the oral microflora and dietary nitrate in regulation of gastric mucosal defense and blood pressure. Rats were treated twice daily with a commercial antiseptic mouthwash while they were given nitrate-supplemented drinking water. The mouthwash greatly reduced the number of nitrate-reducing oral bacteria and as a consequence, nitrate-induced increases in gastric NO and circulating nitrite levels were markedly reduced. With the mouthwash the observed nitrate-induced increase in gastric mucus thickness was attenuated and the gastroprotective effect against an ulcerogenic compound was lost. Furthermore, the decrease in systemic blood pressure seen during nitrate supplementation was now absent. These results suggest that oral symbiotic bacteria modulate gastrointestinal and cardiovascular function via bioactivation of salivary nitrate. Excessive use of antiseptic mouthwashes may attenuate the bioactivity of dietary nitrate.
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