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 F1α (6-keto-PGF1α) in an endothelial cell model, and COX-2 inhibition was based on prostaglandin E 2 (PGE2) in a macrophage model. Radioimmunoassay (RIA) was applied to determine 6-keto-PGF1α in resting human umbilical vein endothelial cell line (ECV304), and PGE2 in activated macrophages. The results showed that the inhibition of 6-keto-PGF 1α yield by Cu-Asp (3 to 0.01 mM) was markedly weaker than that by aspirin (Asp); while the inhibition of PGE2 yield by Cu-Asp (10 to 0.1 mM) was significantly stronger than that by Asp. Based on the inhibition on 6-keto-PGF1α and PGE2, the medium inhibitory concentration (IC50) 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, IC50 (COX-1)/IC50 (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. © 2007 The Pharmaceutical Society of Japan.