Antioxidant activity of nimesulide and its main metabolites.
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 concentration-dependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 mumol/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 mumol/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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Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Italy.
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Aldini
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D013449:Sulfonamides; D017665:Hydroxyl Radical; D006820:Hyaluronic Acid; C012655:nimesulide