Effects of some non-steroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism.
Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.
Roch-Arveiller
M
M
Department of Pharmacology, CNRS URA 595, Hôpital Cochin, Paris, France.
Revelant
V
V
Pham Huy
D
D
Maman
L
L
Fontagne
J
J
Sorenson
J R
JR
Giroud
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010998:Pleurisy / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D012459:Salicylates; D013481:Superoxides; C067228:copper tetrakis(3,5-diisopropylsalicylic acid); C067227:3,5-diisopropylsalicylic acid; D003300:Copper; D001241:Aspirin; D007213:Indomethacin