Suppressive effect of melatonin administration on ethanol‐induced gastroduodenal injury in rats in vivo

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Abstract
Melatonin protection against ethanol‐induced gastroduodenal injury was investigated in duodenum‐ligated rats. Melatonin, injected i.p. 30 min before administration of 1 ml of absolute ethanol, given by gavage, significantly decreased ethanol‐induced macroscopic, histological and biochemical changes in the gastroduodenal mucosa. Ethanol‐induced lesions were detectable as haemorrhagic streaks. Ethanol administration damaged 36% and 25% of the total gastric and duodenal surface, respectively. Melatonin treatment reduced ethanol‐induced gastric and duodenal damage to 14% and 8%, respectively. When indomethacin was given together with ethanol, the gastric damaged area was 44% of the total surface, while the duodenal damaged area was 35%; melatonin administration reduced the damage to only 13% of the total gastric surface and to 12% of total duodenal surface. Both stomach and duodenum of ethanol‐treated animals showed polymorphonuclear leukocyte (PMN) infiltration. The number of PMN increased more than 600 and 200 times in stomach and duodenum, respectively, following ethanol administration. Melatonin treatment reduced ethanol‐induced PMN infiltration by 38% in the stomach and 20% in the duodenum. In indomethacin‐ethanol‐treated rats, the number of PMN increased by 875% compared to control group in the stomach and by 264% in duodenum. Melatonin administration reduced the indomethacin‐ethanol‐induced PMN rise by 57% in the stomach and 40% in the duodenum. Gastroduodenal total glutathione (tGSH) concentration and glutathione reductase (GSSG‐Rd) activity were significantly reduced following ethanol and indomethacin‐ethanol administration. Melatonin ameliorated both the decrease in tGSH concentration as well as the reduction of GSSG‐Rd activity elicited by ethanol both in the stomach and duodenum; melatonin was effective against indomethacin‐ethanol‐induced damage only in the stomach. Ethanol‐induced gastroduodenal damage is believed to be mediated by the generation of free radicals. Recently, a number of in vivo and in vitro experiments have shown melatonin to be an effective antioxidant and free radical scavenger; thus, we conclude that the protection by melatonin against ethanol‐induced gastroduodenal injury is due, at least in part, to its radical scavenging activity. British Journal of Pharmacology (1997) 121, 264–270; doi:10.1038/sj.bjp.0701104