Cytoprotective effects of met-enkephalin and alpha-MSH on ethanol induced gastric lesions in rats

We used the rat model of ethanol induced gastric lesions to measure cytopro tective effects of neuropeptides met-enkephalin and alpha -melanocyte stimu lating hormone (alpha -MSH). The lesions were induced with i.g. application of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol. Sacrifice was made 1 h after ethanol application and hemorrhagic gastric ar ea was assessed in mm(2). alpha -MSH and met-enkephalin exhibited significa nt and additive cytoprotective effects. The protective effects of alpha -MS H were significantly stronger than of met-enkephalin. Almost total absence of lesions was obtained with met-enkephalin and alpha -MSH mixture 10:1 (10 mg/kg met-enkephalin and 1 mg/kg alpha -MSH). The addition of indomethacin (5 mg/kg s.c.) almost completely abolished the effect of met-enkaphalin, w hile alpha -MSH mediated cytoprotectipon was weakened but still present. In terestingly, indomethacin also blocked almost completely the cytoprotective effects of met-enkephalin and alpha -MSH mixture. The latter result may ha ve a practical consequence for the clinical trials in which met-enkephalin and alpha -MSH could be used in combination with non-steroidal anti-inflamm atory drugs. (C) 2001 Elsevier Science Ltd. All rights reserved.