PROSTAGLANDINS AND NITRIC-OXIDE IN COPPER-COMPLEX MEDIATED PROTECTIONAGAINST ETHANOL-INDUCED GASTRIC DAMAGE

This study was designed to determine the effects of oral administratio n of the copper(II) complex of aminoacids, on gastric lesions induced by ethanol in rats and the possible mechanism(s) of protection. The co pper(II) complex of L-tryptophan and L-phenylalanine is reported as th e most effective in reducing ulcer numbers as well as ulcer severity o f the many amino acid complexes studied. We investigated the role of P GE, and nitric oxide (NO) in the protection afforded by Cu(II)(L-Trp)( L-Phe) against ethanol-induced damage. The involvement of endogenous e icosanoids and NO was evaluated with the respective inhibitors of pros taglandin and NO synthesis, indomethacin and N-G-nitro-L-arginine (L-N NA). Ex vivo PGE(2) accumulation in the rat gastric mucosa has also be en determined. Pretreatment with indomethacin only partially counterac ted the protective activity of Cu(II)(L-Trp)(L-Phe). L-NNA did not att enuate the protection by Cu(II)(L-Trp)(L-Phe), which was reduced but n ot prevented by indomethacin, suggesting that prostanoids contribute t o the Cu(II)(L-Trp)(L-Phe) protective effect, together with some mecha nism(s) other than NO synthesis. (C) 1997 The Italian Pharmacological Society.