Anti-inflammatory Activities Of Copper-aspirin Complex And Its Selective Inhibitory Effects On COXs

[Objectives] To study the anti-inflammatory activities of copper-aspirin complex (Cu-Asp) and its selective inhibitory effects on COXs. [ Methods ] The anti-inflammatory effects were investigated on mouse ear swelling induced by xylene, carrageenin-challenged paw edema, turpentine-elicited nitrogen pouch granuloma and acetic acid-caused air pouch synovitis in rats, respectively. Radioimmunoassay (RIA) was applied to determine the levels of 6-keto-prostaglandin F_1α (6-keto-PGF_1α) and prostaglandin E₂ (PGE₂) in human umbilical vein endothelial cells (ECV304) and monocytes, respectively. [ Results ] (1) 50 mg/kg Cu-Asp markedly inhibited inflammatory process of ear swelling induced by xylene in mice in a dose-dependent manner and the median effective dose (ED50) was 81.6 ± 9.7 mg/kg, obtaining an activity similar to that of 200 mg/kg Asp; (2) Cu-Asp 25 to 100 mg/kg markedly suppressed acute paw edema produced by injecting 1% carrageenan, with an effective duration of at least 6 h; the effect of 50 mg/kg Cu-Asp was nearly similar to that of 200 mg/kg Asp; (3) 50 mg/kg Cu-Asp significantly decreased wet and dry weight of pouch granuloma elicited by turpentine and nitrogen, with an activity stronger than that of 200 mg/kg Asp; the ED₅₀ was 87.3 ± 10.1 and 71.3 ± 10.2 mg/kg, respectively; (4) Cu-Asp 50 to 200 mg/kg...