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.
Antioxidant activity of nimesulide and its main metabolites / R. Maffei Facino, M. Carini, G. Aldini. - In: DRUGS. - ISSN 0012-6667. - 46 Suppl 1:1(1993), pp. 15-21.
|Titolo:||Antioxidant activity of nimesulide and its main metabolites|
CARINI, MARINA (Secondo)
ALDINI, GIANCARLO (Ultimo)
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||1993|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2165/00003495-199300461-00005|
|Appare nelle tipologie:||01 - Articolo su periodico|