In Vitro Study of the Antioxidant Properties of Nimesulide and 4-Oh Nimesulide: Effects on Hrp- and Luminol-Dependent Chemiluminescence Produced by Human Chondrocytes
Zheng, S. X.; Mouithys-Mickalad, Ange; Dupont, Ginetteet al.
2000 • In Osteoarthritis and Cartilage, 8 (6), p. 419-25
In Vitro Study of the Antioxidant Properties of Nimesulide and 4-Oh Nimesulide Effects on Hrp- and Luminol-Dependent Chemiluminescence Produced by Human Chondrocytes.pdf
[en] OBJECTIVES: Reactive oxygen species (ROS) are now recognized to play an important role in the pathogenesis of rheumatic diseases and constitute an interesting therapeutic target for drugs. This in vitro study was designed to evaluate the antioxidant properties of nimesulide (NIM), a nonsteroidal antiinflammatory drug of the sulfonanilide class, and its main metabolite 4-OH nimesulide (4-OHNIM). METHODS: The scavenging effects of NIM and 4-OH NIM on hydroxyl radical ((.)OH) and superoxide anions (O(minusd)(2)) were investigated by electron spin resonance (ESR), using 5, 5-dimethylpyrroline-N-oxide (DMPO) as the spin trap agent. The quenching properties of these drugs on hypochlorite anion was studied by luminol enhanced chemiluminescence. Finally, the effects of NIM and 4-OHNIM on the reactive oxygen species production by human articular chondrocytes were recorded by HRP and luminol-enhanced chemiluminescence. RESULTS: By this method it has been demonstrated that NIM and 4-OHNIM, at concentrations ranging from 10 to 100 microM, are potent scavengers of(.)OH whereas only 4-OHNIM was capable to scavenge O(minusd)(2). Chemiluminescence generated by HOCl was also significantly and dose-dependently inhibited by both NIM and 4-OHNIM. Nevertheless, at each concentration tested, the inhibitory effect of 4-OHNIM was significantly more marked, even at the highest concentration (100 microM). Furthermore, when chondrocytes were pre-incubated for 48-96 h with NIM or 4-OHNIM, the luminol- and HRP-dependent CL produced by the cells was significantly inhibited in a dose-dependent manner. CONCLUSIONS: NIM and 4-OHNIM may protect cartilage against oxidative stress, not only by scavenging ROS but also by inhibiting their production by chondrocytes.
Disciplines :
Rheumatology
Author, co-author :
Zheng, S. X.
Mouithys-Mickalad, Ange ; Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Dupont, Ginette ; Université de Liège - ULiège > Centres généraux > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Crielaard, Jean-Michel ; Université de Liège - ULiège > Département des sciences de la motricité > Evaluation et entraînement des aptitudes physiques
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Language :
English
Title :
In Vitro Study of the Antioxidant Properties of Nimesulide and 4-Oh Nimesulide: Effects on Hrp- and Luminol-Dependent Chemiluminescence Produced by Human Chondrocytes
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