In vitro comparative assessment of the scavenging activity against three reactive oxygen species of non-steroidal anti-inflammatory drugs from the oxicam and sulfoanilide families.
The study of the interaction of non-steroidal anti-inflammatory drugs (NSAIDs) with several reactive oxygen species is of great interest in inflammatory conditions where an uncontrolled release of these potentially damaging intermediates has been documented. This study focused on the scavenging of three species (hydroxyl radical, hydrogen peroxide and hypochlorous acid) with several members of the oxicam family and with the sulfoanilide nimesulide. Reaction with hydroxyl radical was assessed by the modified deoxyribose assay, and rate constants were calculated showing values between 0.8 and 1.1 x 10(10) M(-1) s(-1) for oxicams and of about 0.9 x 10(10) M(-1) s(-1) for nimesulide and ibuprofen. These were consistent with those of the literature but in the same range as those for other NSAIDs and for several thiol-containing molecules. The study of hydrogen peroxide scavenging by the horseradish peroxidase (HRP) assay lacked specificity but no interaction could be evidenced by the glutathione peroxidase assay. The scavenging of hypochlorous acid was finally investigated by the recently developed para-aminobenzoic acid assay which demonstrated better performances for meloxicam (1.7 x 10(4) M(-1) s(-1)) as compared to the other oxicams (tenoxicam: 4.0 x 10(4) M(-1) s(-1), piroxicam: 3.6 x 10(4) M(-1) s(-1), lornoxicam: 4.3 x 10(4) M(-1) s(-1)) and nimesulide (2.3 x 10(3) M(-1) s(-1)). These rate constants were, however, lower than those for thiol-containing molecules and ascorbate. These results suggest that the antioxidant properties of NSAIDs could be influenced by a proper pharmacomodulation as far as the scavenging of hypochlorous acid is concerned while the interest is quite limited for the scavenging of hydroxyl radical.
Van Antwerpen
Pierre
P
Laboratory of Pharmaceutical Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Campus Plaine 205-5, B-1050 Brussels, Belgium.
Nève
Jean
J
D000813:Anilides / Q000737:chemistry / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000493:pharmacokinetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species