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 cytoprotective effects of neuropeptides met-enkephalin and alpha-melanocyte stimulating 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 area was assessed in mm(2). alpha-MSH and met-enkephalin exhibited significant and additive cytoprotective effects. The protective effects of alpha-MSH 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, while alpha-MSH mediated cytoprotection was weakened but still present. Interestingly, indomethacin also blocked almost completely the cytoprotective effects of met-enkephalin and alpha-MSH mixture. The latter result may have a practical consequence for the clinical trials in which met-enkephalin and alpha-MSH could be used in combination with non-steroidal anti-inflammatory drugs.