title: Copper-aspirin complex inhibits cyclooxygenase-2 more selectively than aspirin.
abstract: The antiinflammatory effects of the copper-aspirin complex (Cu-Asp) were more potent than that of Asp in rats or mice with fewer classic adverse effects. The aim of this study was to determine the cause by evaluating Cu-Asp selective inhibition on cyclooxygenases (COX). COX-1 inhibition was evaluated based on 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) in an endothelial cell model, and COX-2 inhibition was based on prostaglandin E(2) (PGE(2)) in a macrophage model. Radioimmunoassay (RIA) was applied to determine 6-keto-PGF(1alpha) in resting human umbilical vein endothelial cell line (ECV304), and PGE(2) in activated macrophages. The results showed that the inhibition of 6-keto-PGF(1alpha) yield by Cu-Asp (3 to 0.01 mM) was markedly weaker than that by aspirin (Asp); while the inhibition of PGE(2) yield by Cu-Asp (10 to 0.1 mM) was significantly stronger than that by Asp. Based on the inhibition on 6-keto-PGF(1alpha) and PGE(2), the medium inhibitory concentration (IC(50)) of Cu-Asp on COX-1 and on COX-2 was 1.03+/-0.15 mM, and 0.32+/-0.04 mM, respectively. The selective inhibition index on COX-2, IC(50) (COX-1)/IC(50) (COX-2), of Cu-Asp was 3.33+/-0.89, while that of Asp was 0.42+/-0.12. The results suggest that, unlike Asp, Cu-Asp is a relatively selective inhibitor of COX-2 in the present models; the selectivity of Cu-Asp is about seven-fold greater than that of Asp.
authors.affiliation: Yunnan Pharmacological Laboratories of Natural Products, Kunming Medical College, Western People's Road, Kunming, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yun
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Chun Lan
authors.initials: CL
authors.lastname: Zheng
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Wei Gang
authors.initials: WG
authors.lastname: Duan
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.forename: Jia Qing
authors.initials: JQ
authors.lastname: Ma
authors.forename: Dian Hua
authors.initials: DH
authors.lastname: Wang
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Shen
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D015121:6-Ketoprostaglandin F1 alpha; D003300:Copper; D015232:Dinoprostone; D001241:Aspirin