Antioxidant Activity of Nimesulide and its Main Metabolites

Abstract

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.