|Reference : Potential Antioxidant properties of Aceclofenac and its Metabolites: Investigation on an...|
|Scientific congresses and symposiums : Poster|
|Life sciences : Biochemistry, biophysics & molecular biology|
|Potential Antioxidant properties of Aceclofenac and its Metabolites: Investigation on an in vitro model|
|Mouithys-Mickalad, Ange [Université de Liège - ULg > > Centre de l'oxygène : Recherche et développement (C.O.R.D.) >]|
|Mathy, Marianne [Université de Liège - ULg > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) >]|
|Deby, Carol [ > > ]|
|Lamy, Maurice [Université de Liège - ULg > > Anesthésie et réanimation >]|
|Henrotin, Yves [Université de Liège - ULg > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie >]|
|Deby-Dupont, Ginette [ > > ]|
|The Meeting of the Society for Free Radical Resqearch Europe (SFRR-2001)|
|du 22 juin au 24 juin 2001|
|SFRR- European Region|
|[en] Aceclofenac ; NSAIDs ; Chemiluminescence (CL) ; Electron Spin Resonance (ESR) ; Antioxidant ; PMN|
|[en] Introduction: Recent studies have shown that some steroidal anti-inflammatory drugs (NSAIDs) could exert their actions by multifactorial processes. Among them, the potential antioxidant activity of certain NSAIDs towards various reactive oxygen species (ROS) is often suggested and could have pharmacological relevance.
Objective: This study was designed to assess the potential antioxidant properties (IC50 values) of aceclofenac and its metabolites (4’OH-aceclofenanc and diclofenac) on three different systems of ROS production, using chemiluminescence (CL) technique with luminal and electron spin resonance (ESR) spin trapping.
Material and Methods: Isolated human PMNs (1x106 cells) were activated with 5x10-7 M PMA in the presence of luminal (CL assays) with or without drug addition. For spin trapping experiments, 100 mM DMPO, a radical trapping agent, was added to the reaction milieu containing 6x106 cells/ml. For free-cell experiments, the Fenton’s reagent was used for generation of ·OH and xanthine/xanthine-oxidase system for O2-radicals. The NaOCl-induced CL, amplified by luminal, was used to test the drug effects on HOCl.
Results: On the model of PMA-activated PMNs, 4’OH-aceclofenac exhibited the best antioxidant profile (IC50 = 10 µM) while the effect of the parent drug was less pronounced (IC50 = 100 µM). Diclofenac did not inhibit CL response even at the high dose of 1 mM. Quite similar results were obtained on the NaOCl-induced chemiluminescence, where the efficacy of the drug was as follows: 4’HO-ACE (25 µM) > ACE (1 mM) > DICLO (no effect at 1 mM). By ESR technique, 4’HO-ACE also showed an inhibitory effect (501 µM) on the ROS production by PMA-activated PMN as well as on the ·OH production, while ACE (IC50 = 100 µM) was less efficient and DICLO (IC50 = 1 mM) without significant effect. These findings indicate that beside its anti-inflammatory effects, aceclofenac acts as an antioxidant, at least in part, by the way of its metabolite especially 4’HO-ACE.
|Centre de l’Oxygène, Recherche et Développement - CORD|
|Researchers ; Professionals|
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