Summary
The antioxidant activity of nimesulide and its main metabolites, 4′-hydroxynimesulide (M1) and 2-(4′-hydroxyphenoxy)-4-N-acetylamino-methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH-supported lipid peroxidation in rat liver microsomes (marker MDA formation) and xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid, determined by gel permeation Chromatographic analysis (marker molecular weight distribution). In the lipid peroxidation model, all the compounds inhibited MDA formation in a concentrationdependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 μmol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L].
Nimesulide was more active than its metabolites in preventing OH·-induced depolymerisation of hyaluronic acid, with a 50% effective concentration of approximately 230 μmol/L, which was fairly comparable to that of tenoxicam. This protective effect was due to the OH·-entrapping capacity of the drug, which, in the Fenton-driven model, is easily converted, via OH· attack, to M1 and putatively to 2-hydroxy-4-nitro-methansulfonanilide.
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References
Berti F, Rossoni G, Buschi A, Villa LM, Robuschi M, et al. Ni-mesulide, a nonsteroidal anti-inflammatory drug, displays antianaphylactic and antihistaminic activity in guinea pigs. Drug Investigation 3: 39–47, 1991
Betts WH, Cleland LG. Effect of metal chelators and antiinflam-matory drugs on the degradation of hyaluronic acid. Arthritis and Rheumatism 25: 1469–1476, 1982
Bevilacqua M, Vago T, Beretta A. Nimesulide as inhibitor of superoxide anion production by human polymorphonuclear leukocytes. In Gennazzani et al. (Eds) Pain and reproduction, pp. 265–272, Parthenon Publishing Group, New Jersey, 1988
Capsoni F, Venegoni E, Minonzio F, Ongari AM, Maresca V, et al. Inhibition of neutrophil oxidative metabolism by nimesulide. Agents and Actions 21: 121–129, 1987
Cotgreave IA, Duddy SK, Kass GEN, Thompson D, Moldéus P. Studies on the antiinflammatory activity of Ebselen. Biochemical Pharmacology 38: 649–656, 1989
Dallegri F, Ottonello L, Gati F, Guidi G. Neutrophil oxidative responses. Cell-directed and scavenging actions of the anti-inflammatory drug nimesulide. Drug Investigation 3: 71–74, 1991
Dallegri F, Patrone F, Ballestrero A, Ottonello L, Ferrando F, et al. Inactivation of neutrophil-derived hypochlorous acid by nimesulide: a potential mechanism for tissue protection during inflammation. International Journal of Tissue Reactions 12: 107–111, 1990
Ernster L, Nordenbrand K. Microsomal lipid peroxidation. In Estabrook RW, Pullmann ME (Eds) Methods in enzymology, Vol. 10, pp. 574–580, Academic Press, New York, 1967
Ichihara S, Tomisawa H, Fukazawa H, Tateishi M. Involvement of leukocyte peroxidases in the metabolism of tenoxicam. Biochemical Pharmacology 34: 1337–1338, 1985
Ichihara S, Tomisawa H, Fukazawa H, Tateishi M, Joly R, et al. Oxidation of tenoxicam by leukocyte peroxidases and H2O2 produces novel products. Drug Metabolism and Disposition 17: 463–468, 1989
Janero DR, Burghardt B. Protection of rat myocardial phospholipid against peroxidative injury through superoxide-(xanthine oxidase)-dependent, iron-promoted Fenton chemistry by the male contraceptive gossypol. Biochemical Pharmacology 37: 3335–3342, 1988
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193: 265–275, 1957
Maffei Facino R, Carini M, Brambilla A, Casciarri I, Scaricabarozzi I, et al. Metabolism of nimesulide in man and radical scavenging activity of its main metabolites. Abstract, p. 244, 3rd Interscience World Conference on Inflammation, Montecarlo, March 15–18, 1989
Maffei Facino R, Carini M, Franzoi L, Pirola O, Bosisio E. Phytochemical characterization and radical scavenger activity of flavonoids from Helichrysum italicum G. Don (Compositae). Pharmacological Research 22: 709–721, 1990
Marino O, Casolaro V, Meliota S, Stellato C, Guidi G. Inhibition of histamine release from human Fc RI+ cells by nimesulide. Abstract. XXth Annual Meeting of the European Histamine Research Society, Marburg, Germany, May 8–12, 1991
Mendichi R, Audisio G, Giacometti Schieroni A, Maffei Facino R, Carini M, et al. Degradation of hyaluronic acid: GPC study. International GPC Symposium, San Francisco, Oct 1991
Muller-Peddinghaus R, Wurl M. The amplified chemiluminesc-ence test to characterize antirheumatic drugs as oxygen radical scavengers. Biochemical Pharmacology 36: 1125–1132, 1987
Vigdhal RL, Tukey RH. Mechanisms of action of novel anti-inflammatory drugs diflumidone and R-805. Biochemical Pharmacology 26: 307–311, 1977
Ward A, Brogden RN. Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states. Drugs 36: 732–753, 1988
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Maffei Facino, R., Carini, M. & Aldini, G. Antioxidant Activity of Nimesulide and its Main Metabolites. Drugs 46 (Suppl 1), 15–21 (1993). https://doi.org/10.2165/00003495-199300461-00005
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DOI: https://doi.org/10.2165/00003495-199300461-00005