Abstract
Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte–endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia–reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal–epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.
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References
Halliwell B, Gotteridge JM: Free Radicals in Biology and Medicine. Oxford, Clarendon Press, 1989
Davies KJA: Oxidative Damage and Repair, Chemical, Biological and Medical Aspects. Oxford, Pergamon Press, 1991
Menger MD, Steiner D, Messmer K: Microvascular ischemia-reperfusion injury in striated muscle: significance of “no reflow.” Am J Physiol 263:H1892-H1900, 1992
Arndt H, Kubes P, Granger DN: Involvement of neutrophils in ischemia—reperfusion injury in the small intestine. Klin Wochenschr 69: 1056-1060, 1991
Grisham MB, Hernandez LA, Granger DN: Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 251:G567-G574, 1986
Schmidt H, Schmidt W, Muller T, Bohrer H, Bach A, Gebhard MM, Martin E: Effect of the 21-aminosteroid Tirilasad mesilate on leukocyte adhesion and macromolecular leakage during endotoxemia. Surgery, 121:328-334, 1997
Grisham MB, Granger DN: Neutrophil mediated mucosal injury. Role of reactive oxygen metabolities: Dig Dis Sci 33:6S-15S, 1988
Yamada T, Grisham MB: Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochenschrift 69:988-994, 1991
Steiner DRS, Gonzalez NC, Wood JG: Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia. J Appl Physiol 91:1160-1167, 2001
Han JY, Miura S, Akiba Y, Higuchi H, Kato S, Suzuki H, Yokoyama H, Ishii H: Chronic ethanol stimulation exacerbates microcirculatory damage in rat mesentery after reperfusion. Am J Physiol Gastrointest Liver Physiol 280:G939-G948, 2001
Panes J, Granger DN: Neutrophil generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology 111:981-989, 1996
Gannon B, Carati C: Intestinal vascular organization. In Gastrointestinal Microcirculation, Progress in Applied Microcirculation, Vol. 17. K Messmer, F Hammersen (eds). Basel, Karger, 1990, pp 55-89
Ruh J, Ryschich E, Secchi A, Gebhard MM, Glaser F, Klar E, Herfarth C: Measurement of blood flow in the main arteriole of the villi in rat small intestine with FITC-labeled erythrocytes. Microvasc Res 56:62-69, 1998
Ruh J, Schmidt E, Vogel F, Klar E: Indomethacin-induced disturbances in villous microcirculation in the rat ileum. Microvasc Res 58:137-143, 1999
Ruh J, Vogel F, Schmidt E, Werner M, Klar E, Secchi A, Gebhard MM, Glaser F, Herfarth C: Effects of hydrogen peroxide scavenger catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease. Microvasc Res 59:329-337, 2000
Butcher EC, Weismann IL: Direct fluorescent labeling of cells with fluoresceine or rhodamine isothiocyanate. I. Technical aspects: J Immunol Methods 37:97-108, 1980
Sarelius E, Duling BA: Direct measurement of microvessel hematocrit, red cell flux and velocity and transit time. Am J Physiol 243:H1018-H1026, 1982
Mithöfer K, Schmidt J, Gebhard MM, Buhr HJ, Herfarth C, Klar E: Measurement of blood flow in pancreatic exchange capillaries with FITC-labeled erythrocytes. Microvasc Res 49:33-48, 1995
Zeintl H, Sack FU, Intaglietta M, Messmer K: Computer assisted leukocyte adhesion measurement in intravital microscopy. Int J Microcirc Clin Exp 8:293-302, 1989
Stryer L: Eicosanoid hormones are derived from polyunsaturated fatty acids. In Biochemistry. L Stryer (ed). New York, Freeman, 1995, pp 624-628
Elson CO, Sartor RB, Tnenyson GS, Riddell RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344-1367, 1995
Satoh H, Inada I, Hirata T, Maki Y: Indomethacin produces gastric antral ulcers in the refed rat. Gastroenterology 81:719-725, 1981
Beck WS, Schneider HT, Dietzel K, Nuernberg B, Brune K: Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Arch Toxicol 64:210-217, 1990
Banerjee AK, Peters TJ: Experimental non-steroidal anti-inflammatory drug-induced enteropathy in the rat: similarities to inflammatory bowel disease and effect of thromboxane synthetase inhibitors. Gut 31:1358-1364, 1990
Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 120:365-376, 1989
Yamagiwa S, Yoshida Y, Halder RC, Weerasinghe A, Sugahara S, Asakura H, Abo T: Mechanisms involved in enteropathy induced by administration of nonsteroidal antiinflammatory drugs (NSAIDs). Dig Dis Sci 46:192-199, 2001
Esplugues JV, Whittle BJ: Gastric damage following local intraarterial adminstration of reactive oxygen metabolites in the rat. Br J Pharmacol 97:1085-1092, 1989
Naito Y, Yoshikawa T, Kaneko T, Iinuma S, Nishimura S, Takahashi S, Kondo M: Role of oxygen radicals in indomethacin-induced gastric mucosal microvascular injury in rats. J Clin Gastroenterol 17:S99-S103, 1993
Arndt H, Palitzsch KD, Anderson DC, Rusche J, Grisham MB, Granger DN: Leucocyte—endothelial cell adhesion in a model of intestinal inflammation. Gut 37:374-379, 1995
Benrahmoune M, Therond P, Abedinzadeh Z: The reaction of superoxide radical with N-acetylcysteine. Free Radic Biol Med: 29:775-782, 2000
Rubanyi GM, Vanhoutte PM: Oxygen derived free radicals, endothelium, and responsiveness of vascular smooth muscle tone. Am J Physiol 250:H815-H821, 1986
Holtz J: Peripheral circulation: Fundamental concepts, comparative aspects of control in specific vascular section, and lymph flow. In Comprehensive Human Physiology, From Cellular Aspects to Integration. U Windhorst, R Greger (eds). Berlin, Springer, 1996, pp 1865-1916
Kelly DA, Piasecki C, Anthony A, Dhillon AP, Pounder RE, Wakefield AJ: Focal reducation of villous blood flow in early indomethacin enteropathy: a dynamic vascular study in the rat. Gut 42:366-376, 1998
Cuzzocrea S, Mazzon, E, Costantino G, Serraino I, De Sarro A, Caputi AP: Effects of N-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovas Res 47:537-548, 2000
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Ruh, J., Schmidt, E. & Vogel, F. Effect of N-Acetylcysteine on Microcirculation of Mucosa in Rat Ileum in a Model of Intestinal Inflammation. Dig Dis Sci 48, 882–889 (2003). https://doi.org/10.1023/A:1023087226504
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DOI: https://doi.org/10.1023/A:1023087226504