In vitro study of the antioxidant properties of nimesulide and 4-OH nimesulide: effects on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes
| Autor: | Yves Henrotin, Alain Labasse, A. P. Maroulis, SX Zheng, Christiane Deby, Jean-Michel Crielaard, Jean-Yves Reginster, Maurice L. Lamy, Ginette Deby-Dupont, Ange Mouithys-Mickalad |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cartilage
Articular Male Antioxidant medicine.medical_treatment Cell Culture Techniques Biomedical Engineering medicine.disease_cause Antioxidants Luminol law.invention chemistry.chemical_compound Chondrocytes Rheumatology law Superoxides medicine Humans Orthopedics and Sports Medicine Antioxidant Chondrocytes Nimesulide Chemiluminescence Horseradish Peroxidase Chemiluminescence Aged chemistry.chemical_classification Reactive oxygen species Sulfonamides Dose-Response Relationship Drug Superoxide Hydroxyl Radical Anti-Inflammatory Agents Non-Steroidal Free Radical Scavengers Middle Aged chemistry Biochemistry Luminescent Measurements Hydroxyl radical Female Oxidative stress Nimesulide medicine.drug |
| Zdroj: | Osteoarthritis and Cartilage. 8(6):419-425 |
| ISSN: | 1063-4584 |
| DOI: | 10.1053/joca.1999.0317 |
| Popis: | 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∸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 100μM, are potent scavengers of · OH whereas only 4-OHNIM was capable to scavenge O∸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 (100μM). Furthermore, when chondrocytes were pre-incubated for 48–96h 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. |
| Databáze: | OpenAIRE |
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