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

The gastric injury associated with nonsteroidal anti-inflammatory drug (NSA ID) therapy has been linked to the detrimental effects of the agents on the processes of prostaglandin synthesis, neutrophil (PMN) activation, and oxy gen free radical generation. In the present study, we investigated the in v ivo protective effects of melatonin on indomethacin-induced gastric lesions in the rat. Peroxidation of lipids and changes in the activities of relate d 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 indomethac in administration prevented gastric injury. The mean ulcer indices signific antly (P < 0.05) decreased. Thiobarbituric acid (TBA) reactive substances i n the gastric mucosa as an index of peroxidation, was increased after indom ethacin administration and this increase was inhibited by melatonin. In add ition, pretreatment with melatonin resulted in a significant increase of th e enzymatic GSH-px activity up to the control levers; however, inhibition o f ulceration by melatonin was not associated with a significant reduction i n PMN infiltration. These results suggest that the protection afforded by t he pineal hormone against indomethacin-induced gastric injury may be, in ad dition to other possible mechanisms, to its radical scavenging activity.