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.
Franco
L
L
Institute of Pharmacology, University of Verona, Policlinico di Borgo Roma, Italy.
Velo
G P
GP
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001120:Arginine / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects*; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015777:Eicosanoids / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002614:Chelating Agents; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; C095494:bis(2-benzimidazolyl)thioter copper complex; D019335:Nitroarginine; D009569:Nitric Oxide; D000431:Ethanol; D003300:Copper; D001120:Arginine; D001241:Aspirin; D007213:Indomethacin