A copper-complex reduced gastric damage caused by acetylsalicylic acid and ethanol

We investigated the effect of oral administration of CuNSN, a bis(2-benzimidazolyl) thioether (see structure 1) on gastric lesions induced in rats by acetylsalicylic acid (ASA) or ethanol. The involvement of endogenous eicosanoids and nitric oxide in protection by CuNSN was evaluated with indomethacin and NG-nitro-L-arginine (L-NNA), inhibitors of prostaglandin and NO synthesis respectively. L-arginine and its enantiomer D-arginine were also used. Pretreatment with graded doses of CuNSN inhibited ASA- and ethanol-induced mucosal injury. CuNSN increased PGE2 output in rat ex vivo gastric mucosal pieces after administration of 100 mg/kg of ASA. Pretreatment with indomethacin only partially counteracted the protective activity of CuNSN against ethanol-induced damage. L-NNA did not attenuate the protection by CuNSN, which was reduced but not prevented by indomethacin, suggesting that prostanoids contribute to the CuNSN protective effect, together with some mechanism(s) other than NO synthesis.