Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-05T03:27:40.010Z Has data issue: false hasContentIssue false
  • English
  • Français

Protective effect of dietary nitrate on experimental gastritis in rats

Published online by Cambridge University Press:  09 March 2007

Muriel Larauche ,
Pauline M. Anton ,
Rafaël Garcia-Villar ,
Vassilia Theodorou ,
Jacques Frexinos ,
Lionel Buéno  and
Jean Fioramonti
Muriel Larauche
Affiliation:
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, BP3, 31931 Toulouse cedex 9, France
Pauline M. Anton
Affiliation:
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, BP3, 31931 Toulouse cedex 9, France
Rafaël Garcia-Villar
Affiliation:
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, BP3, 31931 Toulouse cedex 9, France
Vassilia Theodorou
Affiliation:
Department of Physiology, Ecole Supérieure d'Agriculture de Purpan, Toulouse, France
Jacques Frexinos
Affiliation:
Department of Gastroenterology, Rangueil Hospital, Toulouse, France
Lionel Buéno
Affiliation:
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, BP3, 31931 Toulouse cedex 9, France
Jean Fioramonti*
Affiliation:
Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, BP3, 31931 Toulouse cedex 9, France
*
*Corresponding author: Dr J. Fioramonti, fax +33 561 285 145, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Nitrates have long been considered as harmful dietary components and judged responsible for deleterious effects on human health, leading to stringent regulations concerning their levels in food and water. However, recent studies demonstrate that dietary nitrate may have a major role in human health as a non-immune mechanism for host defence, through its metabolism to NO in the stomach. NO is a versatile molecule and although evidence exists showing that administration of low doses of exogenous NO protects against gastrointestinal inflammation, higher NO doses have been shown to exacerbate injury. So, the effect of an ingestion of nitrates in doses corresponding to a normal diet in human consumers on an experimental gastritis induced by iodoacetamide in rats was investigated. During gastritis one of the following compounds was given orally: water; KNO3; the NO donor sodium nitroprusside; the NO scavenger haemoglobin given with either water or KNO3. N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase inhibitor, was administered with either water, iodoacetamide alone, or combined with KNO3. After killing, the stomach was resected and microscopic damage scores, myeloperoxidase and NO synthase activities were determined. Iodoacetamide-induced gastritis was significantly reduced by KNO3 administration, an effect which was reproduced by sodium nitroprusside and reversed by haemoglobin. L-NAME induced gastric mucosal damage in itself, and KNO3 did not prevent the gastritis induced by iodoacetamide associated with L-NAME. In conclusion, dietary nitrate exerts a protective effect against an experimental gastritis in rats by releasing NO in the stomach but such an effect requires the production of endogenous NO.

Keywords

Nitric oxideInflammationDietary nitrateStomach
Type
Research Article
Information
British Journal of Nutrition , Volume 89 , Issue 6 , June 2003 , pp. 777 - 786
Copyright
Copyright © The Nutrition Society 2003

References

Akiba, Y, Nakamura, M, Mori, M, Suzuki, H, Oda, M, Kimura, H, Miura, S, Tsuchiya, M & Ishii, H (1998) Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat. Journal of Clinical Gastroenterology 27, S64–S73.CrossRefGoogle ScholarPubMed
Anton, PM, Theodorou, V, Bertrand, V, Eutamene, H, Aussenac, T, Feyt, N, Fioramonti, J & Buéno, L (2000) Chronic ingestion of a potential food contaminant induces gastrointestinal inflammation in rats: role of nitric oxide and mast cells. Digestive Diseases and Sciences 45, 1842–1849.CrossRefGoogle ScholarPubMed
Benjamin, N, O'Driscoll, F, Dougall, H, Duncan, C, Smith, L, Golden, M & McKenzie, H (1994) Stomach NO synthesis. Nature 368, 502.CrossRefGoogle ScholarPubMed
Bockler, R, Meyer, H & Schlag, P (1983) An experimental study on bacterial colonization, nitrite and nitrosamine production in the operated stomach. Journal of Cancer Research and Clinical Oncology 105, 62–66.CrossRefGoogle Scholar
Bradley, PP, Priebat, DA, Christensen, RD & Rothstein, G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of Investigative Dermatology 78, 206–209.CrossRefGoogle ScholarPubMed
Brown, JF, Keates, AC, Hanson, PJ & Whittle, BJ (1993) Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells. American Journal of Physiology 265, G418–G422.Google ScholarPubMed
Brown, JF, Tepperman, BL, Hanson, PJ & Whittle, BJ (1994) Lipopolysaccharide induces Ca(2+)-independent nitric oxide synthase activity in rat gastric mucosal cells. European Journal of Pharmacology 292, 111–114.Google ScholarPubMed
Bruning-Fann, CS & Kaneene, JB (1993) The effects of nitrate, nitrite and N-nitroso compounds on human health: a review. Veterinary and Human Toxicology 35, 521–538.Google ScholarPubMed
Bush, PA, Gonzalez, NE, Griscavage, JM & Ignarro, LJ (1992) Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine. Biochemical and Biophysical Research Communications 185, 960–966.CrossRefGoogle ScholarPubMed
Calatayud, S, Sanz, MJ, Canet, A, Bello, R, de Rojas, FD & Esplugues, JV (1999) Mechanisms of gastroprotection by transdermal nitroglycerin in the rat. British Journal of Pharmacology 127, 1111–1118.CrossRefGoogle ScholarPubMed
Cavicchi, M, Gibbs, L & Whittle, BJR (2000) Inhibition of inducible nitric oxide synthase in the human intestinal epithelial cell line, DLD-1, by the inducers of heme oxygenase 1, bismuth salts, heme, and nitric oxide donors. Gut 47, 771–778.CrossRefGoogle ScholarPubMed
Clancy, RM & Abramson, SB (1995) Nitric oxide: a novel mediator of inflammation. Proceedings of the Society for Experimental Biology and Medicine 210, 93–101.CrossRefGoogle ScholarPubMed
Clancy, RM, Leszczynska-Piziak, J & Abramson, SB (1992) Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. Journal of Clinical Investigation 90, 1116–1121.CrossRefGoogle Scholar
Cornee, J, Lairon, D, Velema, J, Guyader, M & Berthezene, P (1992) An estimate of nitrate, nitrite and N-nitrosodimethylamine concentrations in French food products or food groups. Sciences des Aliments 12, 155–197.Google Scholar
Craun, GF, Greathouse, DG & Gunderson, DH (1981) Methaemoglobin levels in young children consuming high nitrate well water in the United States. International Journal of Epidemiology 10, 309–317.CrossRefGoogle ScholarPubMed
Dich, J, Järvinen, R, Knekt, P & Penttila, PL (1996) Dietary intakes of nitrate, nitrite and NDMA in the Finnish Mobile Clinic Health Examination Survey. Food Additives and Contaminants 13, 541–552.CrossRefGoogle ScholarPubMed
Dixit, C, Rastogi, L & Dikshit, M (1999) Effect of nitric oxide modulators on pylorus-ligation-induced ulcers in the rat. Pharmacological Research 39, 33–39.CrossRefGoogle ScholarPubMed
Duncan, C, Dougall, H, Johnston, P, Green, S, Brogan, R, Leifert, C, Smith, L, Golden, M & Benjamin, N (1995) Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nature Medicine 1, 546–551.CrossRefGoogle ScholarPubMed
Duncan, C, Li, H, Dykhuizen, R, Frazer, R, Johnston, P, MacKnight, G, Smith, L, Lamza, K, McKenzie, H, Batt, L, Kelly, D, Golden, M, Benjamin, N & Leifert, C (1997) Protection against oral and gastrointestinal diseases: importance of dietary nitrate intake, oral nitrate reduction and enterosalivary nitrate circulation. Comparative Biochemistry and Physiology 118A, 939–948.CrossRefGoogle ScholarPubMed
Dykhuizen, RS, Frazer, R, Duncan, C, Smith, CC, Golden, M, Benjamin, N & Leifert, C (1996) Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. Antimicrobial Agents and Chemotherapy 40, 1422–1425.CrossRefGoogle ScholarPubMed
Fabia, R, Ar'Rajab, A, Johansson, ML, Willen, R, Andersson, R, Molin, G & Bengmark, S (1993) The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat. Scandinavian Journal of Gastroenterology 28, 155–162.CrossRefGoogle ScholarPubMed
Fargeas, MJ, Theodorou, V, Weirich, B, Fioramonti, J & Buéno, L (1996) Decrease in sensitization rate and intestinal anaphylactic response after nitric oxide synthase inhibition in a food hypersensitivity model. Gut 38, 598–602.CrossRefGoogle Scholar
Franco, L, Talamini, G, Carra, G & Doria, D (1999) Expression of COX-1, COX-2, and inducible nitric oxide synthase protein in human gastric antrum with Helicobacter pylori infection. Prostaglandins and Other Lipid Mediators 58, 9–17.CrossRefGoogle ScholarPubMed
Fu, S, Ramanujam, KS, Wong, A, Fantry, GT, Drachenberg, CB, James, SP, Meltzer, SJ & Wilson, KT (1999) Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116, 1319–1329.CrossRefGoogle ScholarPubMed
Gaboury, JP, Niu, XF & Kubes, P (1996) Nitric oxide inhibits numerous features of mast cell-induced inflammation. Circulation 93, 318–326.CrossRefGoogle ScholarPubMed
Green, SJ (1995) Nitric oxide in mucosal immunity. Nature Medicine 1, 515–517.CrossRefGoogle ScholarPubMed
Griscavage, JM, Rogers, NE, Sherman, MP & Ignarro, LJ (1993) Inducible nitric oxide synthase from a rat alveolar macrophage cell line is inhibited by nitric oxide. Journal of Immunology 151, 6329–6337.CrossRefGoogle ScholarPubMed
Grisham, MB, Johnson, GG, Gautreaux, MD & Berg, RD (1995) Measurement of nitrate and nitrite in extracellular fluids: a window to systemic nitric oxide metabolism. Methods 7, 84–90.CrossRefGoogle Scholar
Gurbuz, V, Alican, I, Berrak, , Yegen, C, Bozkurt, A, Oktar, B, Haklar, G, Yuksel, M & Kurtel, H (1999) Role of nitric oxide in indomethacin-induced gastric mucosal dysfunction in the rat. Experimental Physiology 84, 319–332.Google ScholarPubMed
Hara, E, Takahashi, K, Takeda, K, Nakayama, M, Yoshizawa, M, Fujita, H, Shirato, K & Shibahara, S (1999) Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors. Biochemical Pharmacology 58, 227–236.CrossRefGoogle ScholarPubMed
Iikura, M, Takaishi, T, Hirai, K, Yamada, H, Iida, M, Koshino, T & Morita, Y (1998) Exogenous nitric oxide regulates the degranulation of human basophils and rat peritoneal mast cells. International Archives of Allergy and Applied Immunology 115, 129–136.CrossRefGoogle ScholarPubMed
Karmeli, F, Okon, E & Rachmilewitz, D (1996) Sulfhydryl blocker-induced gastric damage is ameliorated by scavenging of free radicals. Gut 38, 826–831.CrossRefGoogle ScholarPubMed
Kato, S, Kitamura, M, Korolkiewicz, RP & Takeuchi, K (1998) Role of nitric oxide in regulation of gastric acid secretion in rats: effects of NO donors and NO synthase inhibitor. British Journal of Pharmacology 123, 839–846.CrossRefGoogle ScholarPubMed
Kimura, H, Miura, S, Shigematsu, T, Ohkubo, N, Tsuzuki, Y, Kurose, I, Higuchi, H, Akiba, Y, Hokari, R, Hirokawa, M, Serizawa, H & Ishii, H (1997) Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease. Digestive Diseases and Sciences 42, 1047–1054.CrossRefGoogle ScholarPubMed
Kitagawa, H, Takeda, F & Kohei, H (1990) Effect of endothelium-derived-relaxing factor on the gastric lesion induced by HCl in rats. Journal of Pharmacological and Experimental Therapeutics 253, 1133–1137.Google ScholarPubMed
Konturek, SK & Konturek, PC (1995) Role of nitric oxide in the digestive system. Digestion 56, 1–13.CrossRefGoogle ScholarPubMed
Kubes, P & Wallace, JL (1995) Nitric oxide as a mediator of gastrointestinal injury? – Say it ain't so. Mediators of Inflammation 4, 397–405.CrossRefGoogle ScholarPubMed
Lalich, JJ (1962) Iodoacetamide-induced gastric ulcer in rats. Proceedings of the Society for Experimental Biology and Medicine 109, 905–908.CrossRefGoogle ScholarPubMed
Lamarque, D & Whittle, BJR (1995) Role of oxygen-derived metabolites in the rat gastric mucosal injury induced by nitric oxide donors. European Journal of Pharmacology 277, 187–194.CrossRefGoogle ScholarPubMed
Larauche, M, Anton, P, Fioramonti, J, Garcia-Villar, R, Theodorou, V & Buéno, L (2000) Gastroenterology 118, A793.CrossRefGoogle Scholar
Li, H, Duncan, C, Townend, J, Killham, K, Smith, LM, Johnston, P, Dykhuizen, R, Kelly, D, Golden, M, Benjamin, N & Leifert, C (1997) Nitrate-reducing bacteria on rat tongues. Applied and Environmental Microbiology 63, 924–930.CrossRefGoogle ScholarPubMed
Lopez-Belmonte, J, Whittle, BJR & Moncada, S (1993) The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. British Journal of Pharmacology 108, 73–78.CrossRefGoogle ScholarPubMed
McCafferty, DM, Mudgett, JS, Swain, MG & Kubes, P (1997) Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology 112, 1022–1027.CrossRefGoogle Scholar
McKnight, GM, Smith, LM, Drummond, RS, Duncan, CW, Golden, M & Benjamin, N (1997) Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans. Gut 40, 211–214.CrossRefGoogle ScholarPubMed
MacNaughton, WK, Cirino, G & Wallace, JL (1989) Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Science 45, 1869–1876.CrossRefGoogle ScholarPubMed
Meah, MN, Harrison, N & Davies, A (1994) Nitrate and nitrite in foods and the diet. Food Additives and Contaminants 11, 519–532.CrossRefGoogle ScholarPubMed
Mendez, A, Fernandez, M, Barrios, Y, Lopez-Coviella, I, Gonzales-Mora, JL, Del Rivero, M, Salido, E, Bosch, J & Quintero, E (1997) Constitutive NOS isoforms account for gastric mucosal NO overproduction in uremic rats. American Journal of Physiology 272, G894–G901.Google ScholarPubMed
Miller, MJ, Munshi, UK, Sadowska-Krowicka, H, Kakkis, JL, Zhang, XJ, Eloby-Childress, S & Clark, DA (1994) Inhibition of calcium-dependent nitric oxide synthase causes ileitis and leukocytosis in guinea pigs. Digestive Diseases and Sciences 39, 1185–1192.CrossRefGoogle ScholarPubMed
Moncada, S, Palmer, RMJ & Higgs, EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Reviews 43, 109–142.Google ScholarPubMed
Mourad, FH, Khuri, M, Shouaib, F & Nassar, CF (2000) Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats. European Journal of Gastroenterology and Hepatology 12, 81–84.CrossRefGoogle ScholarPubMed
Nahavandi, A, Dehpour, AR, Mani, AR, Homayounfar, H & Abdoli, A (1999) NG-nitro-L-arginine methylester is protective against ethanol-induced gastric damage in cholestatic rats. European Journal of Pharmacology 370, 283–286.CrossRefGoogle ScholarPubMed
Nakajima, S, Arizono, N, Hattori, T & Bamba, T (1996) Increase in mucosal and connective tissue-type mast cells in the stomach with acetic acid-induced ulcer in rats. Acta Pathologica, Microbiologica et Immunologica Scandinavica 104, 19–29.CrossRefGoogle Scholar
Nakajima, S, Krishnan, B, Ota, H, Segura, AM, Hattori, T, Graham, DY & Genta, RM (1997) Mast cells involvement in gastritis with or without Helicobacter pylori infection. Gastroenterology 113, 746–754.CrossRefGoogle ScholarPubMed
Nishida, K, Ohta, Y & Ishiguro, I (1998) Changes in nitric oxide production with lesion development in the gastric mucosa of rats with water immersion restraint stress. Research Communications in Molecular Pathology and Pharmacology 100, 201–212.Google ScholarPubMed
Ohta, H, Tanoue, K, Tarnawski, AS, Pai, R, Itani, RM, Sander, FC, Sugimachi, K & Sarfeh, IJ (1997) Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: a key to increased susceptibility to damage? Gastroenterology 112, 1920–1930.CrossRefGoogle Scholar
Pique, JM, Whittle, BJ & Esplugues, JV (1989) The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. European Journal of Pharmacology 174, 293–296.CrossRefGoogle ScholarPubMed
Polte, T, Abate, A, Dennery, PA & Schroder, H (2000) Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arteriosclerosis, Thrombosis and Vascular Biology 20, 1209–1215.CrossRefGoogle ScholarPubMed
Potter, CL & Hanson, PJ (2000) Exogenous nitric oxide inhibits apoptosis in guinea pig gastric mucous cells. Gut 46, 156–162.CrossRefGoogle ScholarPubMed
Qiu, BS, Pfeiffer, CJ & Cho, CH (1996) Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. Digestion 57, 60–66.CrossRefGoogle ScholarPubMed
Rachmilewitz, D, Karmeli, F, Eliakim, R, Stalnikowicz, R, Ackerman, Z, Amir, G & Stamler, JS (1994) Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients. Gut 35, 1394–1397.CrossRefGoogle ScholarPubMed
Radomski, MW, Palmer, RM & Moncada, S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet ii, 1057–1058.CrossRefGoogle Scholar
Rengasamy, A & Johns, RA (1993) Regulation of nitric oxide synthase by nitric oxide. Molecular Pharmacology 44, 124–128.Google ScholarPubMed
Rouzade, ML, Anton, P, Fioramonti, J, Garcia-Villar, R, Theodorou, V & Buéno, L (1999) Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats. Alimentary Pharmacology and Therapeutics 13, 1235–1241.CrossRefGoogle ScholarPubMed
Spiegelhalder, B, Eisenbrand, G & Preussman, R (1976) Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food and Cosmetics Toxicology 14, 545–548.CrossRefGoogle ScholarPubMed
Szabo, S, Trier, JS & Frankel, PW (1981) Sulfhydryl compounds may mediate gastric cytoprotection. Science 214, 200–202.CrossRefGoogle ScholarPubMed
Tannenbaum, SR, Weisman, M & Fett, D (1976) The effect of nitrate intake on nitrite formation in human saliva. Food and Cosmetics Toxicology 14, 549–552.CrossRefGoogle ScholarPubMed
Tepperman, BL & Soper, BD (1994) Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol. Canadian Journal of Physiology and Pharmacology 72, 1308–1312.CrossRefGoogle ScholarPubMed
Vittozzi, L (1992) Toxicology of nitrates and nitrites. Food Additives and Contaminants 9, 579–585.CrossRefGoogle ScholarPubMed
Wakulich, CA & Tepperman, BL (1997) Role of glutathione in nitric oxide-mediated injury to rat gastric mucosal cells. European Journal of Pharmacology 319, 333–341.CrossRefGoogle ScholarPubMed
Walker, R (1994) The conversion of nitrate into nitrite in several animal species and man. In Health Aspects of Nitrate and its Metabolites (Particularly Nitrite), pp. 115–123. Proceedings of an International Workshop, Bilthoven (Netherlands), pp. 115–123. Strasbourg, France: Council of Europe Press.Google Scholar
Walters, CL & Smith, PLR (1981) The effect of water-borne nitrate on salivary nitrite. Food and Chemical Toxicology 19, 297–302.CrossRefGoogle ScholarPubMed
Wang, WP, Guo, X, Koo, MWL & Cho, CH (2000) The protective effect of heme oxygenase-1 induction on the experimental colitis induced by trinitrobenzene sulfonic acid in rats. Gastroenterology 118, A579.CrossRefGoogle Scholar
Ward, FW, Coates, ME & Walker, R (1986) Nitrate reduction, gastrointestinal pH and N-nitrosation in gnotobiotic and conventional rats. Food and Chemical Toxicology 24, 17–22.CrossRefGoogle ScholarPubMed
Wei, XQ, Charles, IG, Smith, A, Ure, J, Feng, GJ, Huang, FP, Xu, D, Muller, W, Moncada, S & Liew, FY (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375, 408–411.CrossRefGoogle ScholarPubMed
Witter, JP, Balish, E & Gatley, SJ (1979) Distribution of nitrogen-13 from labeled nitrate and nitrites in germfree and conventional-flora rats. Applied and Environmental Microbiology 38, 870–878.CrossRefGoogle ScholarPubMed
World Health Organization (1962) Evaluation of the toxicity of a number of antimicrobials and antioxidants (Sixth report of the Joint FAO/WHO Expert Committee on Food Additives). WHO Technical Report Series no. 228, pp. 73–76. Geneva, Switzerland: WHO.Google Scholar
World Health Organization (1987) Principles for the safety assessment of food additives and contaminants in food. WHO Environmental Health Criteria no. 70. Geneva, Switzerland: WHO.Google Scholar
Yasin, R & Leese, CL (1970) The production of chronic gastritis and ulceration in the glandular stomach of rats by iodoacetamide. European Journal of Cancer 6, 425–432.CrossRefGoogle ScholarPubMed