Action of the 4-Nitro-2-Phenoximethanesulphonanilide (Nimesulide) on Neutrophil Chemotaxis and Superoxide Production
Palavras-chave:
neutrophil, superoxide, chemotaxis, 4-nitro-2-phenoximethanesulphonanilideResumo
O 4-nitro-2-fenoximetanosulfonanilide (nimesulide), antiinflamatório não esteróide, vem sendo utilizado no tratamento de quadros inflamatórios devido à sua atividade farmacológica nestes mecanismos de resposta as injúrias flogísticas. O objetivo do presente trabalho é estudar a ação deste fármaco sobre duas importantes funções neutrofílicas: quimiotaxia e produção de ânion superóxido após pré incubação com doses crescentes da droga (0,1; 0,3 e 0,5mM). Os resultados obtidos demonstram que a pré-incubação de PMNs coletados do sangue periférico de indivíduos normais com o 4-nitro-2-fenoximetanosulfonanilide reduz significativamente a produção de superóxido por estimulação de PMN com acetato de forbol miristato (PMA 50ng/ml). formil metionil leucil fenilalanina (FMLP 10-'M e Zimozan opsonizado (1mg/ml). Adicionalmente o fármaco se mostrou igualmente efetivo em reduzir a habilidade quimiotáxica de PMNs, frente ao fator C5a (2% de soro ativado por zimozan). FMLP (10-9M) e leucotrieno B4 (3x10-'M). Os resultados obtidos sugerem que além da sua atividade a nível do metabolismo do ácido araquidônico, o 4-nitro-2-fenoximetanosulfonanilide possa interferir diretamente sobre a função neutrofílica, o que provavelmente contribui para sua ação antiinflamatória.
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. ABRAMSON, S.; EDELSON, H.; KAPLAN, H .; LUDEEWIG, R. & WEISSMANN, G. - Inhibition of neutrophil activation by non-steroidal anti-inflammatory drugs. Am J Med, 74: 3-6, 1984.
ANDERSON, T.; KAHIGREN, C.; LEW, P. D. & STENDAHL, O. - Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to cahges in the cytosolic free Ca Level and action of phorbol myristate acetate. J Clin Invest, 79: 1226-1233, 1987.
BABIOR, B. M. - Owygen-dependent microbial killing by phagocytes. N Engl Med J, 298: 659-668, 1978.
BABIOR, B. M.; CURNUTTE, J. T. & MCMURRICH, B. J. - The particulate superoxideforming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst. J Clin Invest, 58: 989-996, 1976.
BABIOR, B. M.; KIPNES, R. S. & CURNUTTE, J. T. - Biological defenses mechanism. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest, 52: 741-744, 1973.
BAGGIOLINI, M. & KERNEN, P. - Neutrophil activation, control of shape change, exocytosis and respiratory burst. NIPS, 7: 215-219, 1982.
BAGGIOLINI, M.; BOULAY, F.; BADLEY, J. A. & CURNUTTE, J. T. - Activation of neutrophil leukocytes: chemoattractant receptors and respiratory burst. FASEB, 7: 1004-1010, 1993.
BATES, E. J.; LOWTHER, D. A. & HANDLEY, C. J. - Oxygen free-radicals mediate and inhibition of proteoglycan synthesis in cultured articular cartilage. Ann Rheum Dis, 43: 462-469, 1984.
BEBILACQUA,M.; VAGO, T.&BERETTA,A.-Nimesulide as an inhibitor of superoxide anion (02) production by human polymorphonuclear leukocytes. in Frontiers in gynecological series - Pain and Reproduction. A. R. GENAZZANI, G. NAPPI, F. FACCHINETTI, E. MARTIGNOMI. ed. The Parthenon publishing Group, New Jersey, USA, 265-272, 1987.
BEBILACQUA, M.; NORBIATO, G.; BALDI, G.; BERTORA, P.; VAGO, T. & CHEBAT, E. - Activation of protein kinase C by respiratory burst stimalats desensitizes beta2-adrenoreceptores on human neutrophils. Drug Invest, 3: 54-65, 1991.
BOYUM, A. -Isolation of mononuclear cells and granuloccytes from human blood. J Clin Lab Invest, 21: 77-89, 1968.
CAPSONIJ, F.; VENEGONI, E.; MINONZIO, F.; ONGARI, A. M.; MARESCA, V. & ZANUSSI, C. - Inhibition of neutrophil oxidative matabolism by Nimesulide. Agents Act, 21: 121-129, 1987.
CARR, D. P.; HENN, R.; GREEN, J. R. & BOTTCHER, I. - Comparison of the systemic inhibitor of thromboxane synthesis anti-inflammatory activity and gastro-intestinal toxicity of non-steroidal anti-inflammatory drugs in the rat. Agents Act, 19: 374-375, 1986.
CESERANI, R.; CASCIARRI, I.; CAVALLETTI, E. & CAZZULANI, P. - Action of Nimesulide on rat gastric prostaglandins and renal function. Drug Invest, 3: 14-21, 1991.
CHENOWETH, D. E. & HUGLI, T. E. - Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes. Proc Natl Acad Sci USA, 75: 3943-3947, 1978.
CROSS, C. E.; HALLIWELL, B.; BORISH., E. T.; PRIOR, W. A.; AMES, B. N.; SAUL, R. L.; MCCORD, J. M. & HARMAN, D. - Oxigen radicals and human disease. Ann Intern Med, 107: 526-545, 1987.
CURNUTTE, J. T. & BABIOR, B. M. - Biological defense mechanism. The effect of bacteria and serum on superoxide production by granuloccytes. J Clin Invest, 53: 1662-1672, 1974.
DALLEGRI, F.; OTOONELLO, L.; GATTI, F. & GUIDI, G. - Neutrophil oxidative responses: Cell-directed and scavenging actions of anti-inflammatory drug Nimesulide. Drug Invest, 3(2): 71-74, 1991.
DE CHATELET, L. R.; SHIRLEY, P. S. & JOHNSTON, JR. R. B. - Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes. Blood, 47: 545-554, 1976.
DEL MAESTRO, R. T. - An approach to free radicals in medicine and biology. Acta Physiol Scand, 492: 153-168, 1980.
DEWALD, B.; BAGGLIOLINI, M.; CURNUTTE, J. T. & BABIOR, B. M. - Subcellular localization of the superoxide forming enzyme in human neutrophils. J Clin Invest, 63:21-29, 1979.
FANTONE, C. J. & WARD, P. A. - Role of wxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol, 107(3): 397-418, 1982.
FREEMAN, B. A. & CRAPO, J. D. - Biology of disease - Free radicals and tissue injury. Lab Invest, 17: 412-425, 1982.
GREEWALD, R. A. & MOY, W. W. - Effect of oxygendreived free radicals on hyaluronic acid. Arthritis Rheum, 23: 455-459, 1980.
LAURINDO, I. M. M.; MELLO, S. B. V. & COSSERMELLI, W. - Participação dos radicais livres de oxigênio na fisiopatologia da artrite reumatóide. Rev Hosp Clin Fac Med S Paulo, 47: 38-45, 1992.
LEGFELDER, E. - Can anti-inflammatory drugs act as scavengers of oxygen radicals? Agents Actions, 15: 56-57, 1984.
LEHRER, R. I. & COHEN, L. - Receptor-mediated regulation of superoxide production in human neutrophils stimulated by phorbol myristate acetate. J Clin Invest, 68: 1314-1320, 1981.
MAGNI, E. - Nimesulide, an overview. Drug Invest, 3: 1-3, 1991.
MELLO, S. B. V.; FARSKY, S. H. P.; SANNOMYIA, P. & GARCIA-LEME, J. - Inhibition of neutrophil chemotaxis associated with a plasma protein in aging rats: selective depression of cell responses mediated by complement-derived chemo attractants. J Leuk Biol, 51: 46-52, 1992.
MINTA, J. O. & WILLIAM, M. D. - Some nonsteroidal anti-inflammatory drugs inhibit the generation of superoxide anions by activated polymorphs by blocking ligand-receptor interactions. J Rheum, 12: 752-757, 1985.
MONBOISSE, J. C.; BRAQUET, P. & BOREL, J. P. - Oxygen-free radical as mediators of collagen breakage. Agents Actions, 15: 48-50, 1984.
MONCADA, S.; HERMAN, A. G. & VANHOUTTE, P. - Endothelium-derived relaxing factor is identified as nitrio oxide. TIPS, 8: 365-371, 1987.
SIMPSON, P. J. & LUCCHESI, B. R. - Free radicals and myocardial ischemia and reperfusion injury. J Lab Clin Med, 110: 13-25, 1987.
SWINGLE, K. F. & MOORE, G. G. I. - Pre-clinical pharmacological studies with Nimesulide. Drugs Under Exp Clin Res, 10: 587-597, 1984.
TAUBER, A. I. - Protein kinase C and the activation of the human neutrophil NADPH-oxidase. Blood, 69: 711-720, 1987.
VAN GELDER, B. F. & SLATER, E. C. - The extinction coefficient of cytochrome. Bloch Biophis Acta, 58: 593-595, 1962.
WEENING, R. S.; WEVER, R. & ROOS, D. - Quantitative aspects of the production of superoxide radicals by phagocytising human granulocytes. J Lab Clin Med, 85: 245-252, 1975.
WEISS, S. J. & WARD, P. A. - Immune complex induced generations of oxygen metabolites by human neutrophil. J Immunol, 129: 309-313, 1982.
WILLIAMS, L. T.; SNYDERMAN, R.; PIKE, M. C. & LEKOWITZ, R. L. - Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Nat Acad Sol USA, 74: 1204-1208, 1977.
ZIGMOND, S. H. & HIRSH. J. G. - Leukocyte locomotion and chemotaxis: new method for evaluation and demonstration of cell-derived chemotactic factor. J Exp Med, 137: 387-410, 1973.
WILHELMS, O. H.; LINSSEN, M. J.; LIPPONER, L. & SEILNACHT, W. - Nimesulide, indomethacin. BW 755 C, phenidon, mepacrin and nedocromil inhibit the activation of human and rat leukocytes. Int J Tiss Reac, XII: 101-106, 1990.
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