Abstract
The participation of xanthine-xanthine oxidaseand neutrophils in the development of acute gastricmucosal lesions was examined in rats injected once withcompound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound48/80 injection and developed at 3 hr. The formation ofgastric mucosal lesions at 0.5 hr after compound 48/80injection was prevented by pretreatment with anti-neutrophil antiserum and NPC 14686, anantiinflammatory agent, but not with allopurinol, axanthine oxidase inhibitor. The development of gastricmucosal lesions at 3 hr after compound 48/80 injection was prevented by pretreatment withanti-neutrophil antiserum, NPC 14686, or allopurinol.Increases in the activities of gastric mucosal xanthineoxidase and myeloperoxidase, an index of neutrophilinfiltration, and the content of lipid peroxide occurred 0.5hr after compound 48/80 injection, and these increaseswere enhanced at 3 hr. The increases in gastric mucosalmyeloperoxidase activity and lipid peroxide content at 0.5 hr after compound 48/80injection were attenuated by pretreatment withanti-neutrophil antiserum and NPC 14686, while only theincrease in gastric mucosal xanthine oxidase activity atthe same time point was arrested by allopurinolpretreatment. The increases in gastric mucosal xanthineoxidase and myeloperoxidase activities and lipidperoxide content at 3 hr after compound 48/80 treatment were attenuated by pretreatment withanti-neutrophil antiserum, NPC 14686, or allopurinol.When compound 48/80-injected rats were treated withallopurinol at 0.5 hr after compound 48/80 injection,the progression of gastric mucosal lesions at 3 hr after theinjection was almost completely prevented withinhibition of the increases in gastric mucosal xanthineoxidase and myeloperoxidase activities and lipidperoxide content. These results indicate that in ratswith a single compound 48/80 treatment neutrophilsinfiltrated into the gastric mucosa participated in thedevelopment of acute gastric mucosal lesions and that the xanthine-xanthine oxidase system in thegastric mucosa participated in the progression ratherthan the formation of the gastric mucosallesions.
Similar content being viewed by others
REFERENCES
Ohta Y, Kobayashi T, Nishida K, Ishiguro I: Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recove ry of lesions in gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. Dig Dis Sci 42:1221–1232, 1997
Itoh M, Guth PH: Role of oxyge n-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat. Gastroenterology 88:1162–1167, 1985
Smith SM, Grisham MB, Kvietys PR, Manci EA, Granger MD, Russell JM: Gastric mucosal injury in the rat. Role of iron and xanthine oxidase. Gastroenterology 92:950–956, 1987
Yoshikawa T, Ueda S, Nito Y, Takahashi S, Oyamada H, Morita Y, Yoneta T, Kondo M: Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia—repe rfusion in rats. Free Radic Res Commun 7:285–291, 1989
Wada K, Kamisaki Y, Kitano M, Nakamoto K, Itoh T: Protective effect of cystathionine on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Eur J Pharmacol 294:377–382, 1995
Smith SM, Holm-Rutili L, Perry MA, Grisham MB, Arfors K-E, Granger DN, Kvietys PR, Russell JM: Role of neutrophils in hemorrhagic shock-induced gastric mucosal injury in the rat. Gastroenterology 93:466–471, 1987
Iwai A, Itoh M, Yokoyama Y, Yasue N, Kawai T, Matsuba S, Okayama N, Ishikawa S, Katoh N, Takeuchi T, Sendo F: Role of neutrophils-derived oxygen radicals for the formation of rat gastric mucosal injury by ischemia-reinfusion. Jpn J Gastroenterol (Nippon Shokakibyo Gakkai Zasshi) 88:117–124, 1991
Takahashi A, Nakano M, Nagamachi Y, Inaba H: Detection of O2 2 generate d in the rat gastric mucosa in situ during repe rfusion following ischemia. J Clin Biochem Nutr 17:35–45, 1994
Andrewas FJ, Malcontenti C, O'Brien PE: Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites. Dig Dis Sci 37:1356–1361, 1992
Tanaka J, Yuda Y: Role of lipid peroxidation in gastric mucosal lesions induced by ischemia-reperfusion in the pylorusligated rat. Biol Pharm Bull 16:29–32, 1993
Andrews FJ, Malcontent-Wilson C, O'Brien PE: Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia-reperfusion. Am J Physiol 266:G48–G54, 1994
Wada K, Kamisaki Y, Kitano M, Kishimoto Y, Nakamoto K, Itoh T: A new gastric ulcer model induced by ischemiarepe rfusion in the rat: Role of leukocyte s on ulceration in rat stomach. Life Sci 59:PL295–PL301, 1996
Kushimoto S, Okajima K, Okabe H, Binder BR: Role of granulocyte elastase in the formation of hemorrhagic shockinduced gastric mucosal lesions in the rat. Crit Care Med 24:1041–1046, 1996
Andrews FJ, Malcontenti-Wilson C, O'Brien PE: Expression of adhesion molecules and leukocyte recruitment into gastric mucosa following ischemia–reperfusion. Dig Dis Sci 42:326–332, 1997
Massey V, Komai H, Plamer G: On the me chanism of inactivation of xanthine oxidase by allopurinol and other pyrazole[ 3,4-d]pyrimidines. J Biol Chem 245:2837–2844, 1970
Burch R, Weitzberg M, Blok N, Muhlhauser R, Martin D, Famer SG, Bator JM, Conner JR, Ko C, Kuhn W, McMillan BA, Raynor M, Shearer BG, Tiffany C, Wilkins DE: N-(Fluorenyl-9-me thoxycarbonyl)amino acids, a class of antiinflammatory age nts with different me chanism of action. Proc Natl Acad Sci USA 88:355–359, 1991
Hashimoto S: New spectrophotometeric assay of xanthine oxidase in crude tissue homogenate. Anal Biochem 62:426–433, 1974
Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T: Assay me thod for meyloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 132:345–353, 1983
Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxide s in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:353–358, 1979
Shibata K, Onodera M, Kwada T, Iwai K: Simultaneous microdete rmination of serotonin and 5-hydroxyindole-3-acetic acid with 5-hydroxy-Nv-methyltryptamine, as an internal standard, in biological mate rials by high-performance liquid chromatography with e lectrochemical detection. J Chromatogr 430:381–387, 1988
Enerback L, Lundin PM: Ultrastructure of mast cells in normal and compound 48/80-tre ated rats. Cell Tissue Res 150:95–105, 1974
Befus AD, Pearge FL, Gauldie J, Horsewood P, Bienenstock J: Mucosal mast cells. I. Isolation and functional characteristics of rat intestinal mast cells. J Immunol 128:2475–2480, 1982
Irman-Florjanc T, Erjavec F: Compound 48/80 and substance P induced re lease of histamine and serotonin from peritoneal mast cells. Agents Actions 13:138–141, 1983
Arnould T, Michiels C, Remacle J: Increased PMN adherence on endothelial ce lls after hypoxia: involvement of PAF, CD18/CD 11b, and ICAM-1. Am J Physiol 264:C1102–C1110, 1993
Arnould T, Michiels C, Janssens D, Delaive E, Remacle J: Hypoxia induces PMN adherence to umbilical vein endothelium. Cardiovasc Res 30:1009–1016, 1995
Yoshida N, Yoshikawa T, Nakamura Y, Sakamoto K, Takenaka S, Boku Y, Kassai K, Kondo M: Interaction of neutrophils and endothelial cells under low flow conditions in vitro. Shock 8:125–130, 1997
Kozol R, Kopatsis A, Fligiel SE, Czanko R, Callewaert D: Neutrophil-mediated injury to gastric mucosal surface cells. Dig Dis Sci 39:138–144, 1994
Suzuki M, Grisham MB, Granger DN: Leukocyte-endothelial ce ll adhe sive interactions: Role of xanthine oxidase-derived oxidants. J Leukocyte Biol 50:488–494, 1991
Palluy O, Morliere L, Gris JC, Bonne C, Modat G: Hypoxia/ reoxygenation stimulates endothelium to promote neutrophil adhesion. Free Radic Biol Med 13:21–30, 1992
Kurose I, Argenbright LW, Wolf R, Lianxi L, Granger DN: Ischemia/reperfusion––induce d microvascular dysfunction: Role of oxidants and lipid mediators. Am J Physiol 272:H2976–H2982, 1997
Wakabayashi Y, Fujita H, Morita I, Kawaguchi H, Murota S: Conversion of xanthine dehydrogenase to xanthine oxidase in bovine carotid endothelial cells induced by activated neutrophils: involvement of adhesion molecules. Biochim Biophys Acta 1265:103–109, 1995
Naito Y, Yoshikawa T, Matsuyama K, Yagi N, Arai M, Nakamura Y, Kaneko T, Yoshida N, Kondo M: Neutrophils, lipid peroxidation, and nitric oxide in gastric reperfusion injury in rats. Free Radic Biol Med 24:494–502, 1998
Rights and permissions
About this article
Cite this article
Ohta, Y., Kobayashi, T. & Ishiguro, I. Participation of Xanthine-Xanthine Oxidase System and Neutrophils in Development of Acute Gastric Mucosal Lesions in Rats with a Single Treatment of Compound 48/80, a Mast Cell Degranulator. Dig Dis Sci 44, 1865–1874 (1999). https://doi.org/10.1023/A:1018803025043
Issue Date:
DOI: https://doi.org/10.1023/A:1018803025043