Antioxidant activity and inhibition of human neutrophil oxidative burst mediated by arylpropionic acid non-steroidal anti-inflammatory drugs.
It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. Therefore, the aim of the present work was to evaluate and compare the potential scavenging activity for an array of ROS (O2*-, H2O2, HO*, ROO* and HOCl) and RNS (*NO and ONOO-) using in vitro non-cellular screening systems as well as a cellular screening system (human neutrophil oxidative burst), mediated by the arylpropionic acid derivatives (APAs) NSAIDs ibuprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, naproxen and indoprofen. The results obtained in the present work demonstrate that under the present experimental conditions, many of the studied APA NSAIDs showed O2*- scavenging activity (fenbufen approximately equal to flurbiprofen approximately equal to indoprofen approximately equal to ketoprofen), H2O2 (ketoprofen approximately equal to indoprofen approximately equal to fenbufen>flurbiprofen>naproxen), HO* (fenoprofen approximately equal to ibuprofen>fenbufen approximately equal to flurbiprofen>ketoprofen>indoprofen approximately equal to naproxen), *NO (indoprofen>naproxen), ONOO- (indoprofen>naproxen>fenoprofen approximately equal to flurbiprofen approximately equal to ibuprofen), as well as inhibit myeloperoxidase (MPO) activity (indoprofen) and scavenge human neutrophil derived ROS (ketoprofen>indoprofen>fenbufen>flurbiprofen). The observed effects, if confirmed in vivo, may strongly contribute to the anti-inflammatory therapeutical activity observed with these NSAIDs.
Costa
David
D
REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Portugal.
Moutinho
Luís
L
Lima
José Luís Fontes Costa
JL
Fernandes
Eduarda
E
D000166:Acridines / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008165:Luminol / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000166:Acridines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D011422:Propionates; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; D009195:Peroxidase; C029658:propionic acid; D013755:Tetradecanoylphorbol Acetate