Protective effect of melatonin on indomethacin-induced gastric injury in rats.

The gastric injury associated with nonsteroidal anti-inflammatory drug (NSAID) therapy has been linked to the detrimental effects of the agents on the processes of prostaglandin synthesis, neutrophil (PMN) activation. and oxygen free radical generation. In the present study, we investigated the in vivo protective effects of melatonin on indomethacin-induced gastric lesions in the rat. Peroxidation of lipids and changes in the activities of related enzymes such as glutathione peroxidase (GSH-px) and myeloperoxidase (MPO), as a marker of PMNs infiltration, were also studied. Intraperitoneal (i.p.) injection of melatonin (0.25. 0.5, 1 mg kg(-1)) 30 min before indomethacin administration prevented gastric injury. The mean ulcer indices significantly (P < 0.05) decreased. Thiobarbituric acid (TBA) reactive substances in the gastric mucosa as an index of peroxidation, was increased after indomethacin administration and this increase was inhibited by melatonin. In addition, pretreatment with melatonin resulted in a significant increase of the enzymatic GSH-px activity up to the control levels; however, inhibition of ulceration by melatonin was not associated with a significant reduction in PMN infiltration. These results suggest that the protection afforded by the pineal hormone against indomethacin-induced gastric injury may be, in addition to other possible mechanisms, to its radical scavenging activity.