Prostaglandins and nitric oxide in copper-complex mediated protection against ethanol-induced gastric damage

This study was designed to determine the effects of oral administration of the copper(II) complex of amino acids, on gastric lesions induced by ethanol in rats and the possible mechanism(s) of protection. The copper(II) complex of L-tryptophan and L-phenylalanine is reported as the most effective in reducing ulcer numbers as well as ulcer severity of the many amino acid complexes studied. We investigated the role of PGE2 and nitric oxide (NO) in the protection afforded by Cu(II)(L-Trp)(L-Phe) against ethanol-induced damage. The involvement of endogenous eicosanoids and NO was evaluated with the respective inhibitors of prostaglandin and NO synthesis, indomethacin and NG-nitro-L-arginine (L-NNA). Ex vivo PGE2 accumulation in the rat gastric mucosa has also been determined. Pretreatment with indomethacin only partially counteracted the protective activity of Cu(II)(L-Trp)(L-Phe). L-NNA did not attenuate the protection by Cu(II)(L-Trp)(L-Phe), which was reduced but not prevented by indomethacin, suggesting that prostanoids contribute to the Cu(II)(L-Trp)(L-Phe) protective effect, together with some mechanism(s) other than NO synthesis.