The protective action of melatonin on indomethacin-induced gastric and testicular oxidative stress in rats.

Reactive oxygen species and lipid peroxidation play a role in the pathogenesis induced by the non-steroidal anti-inflammatory drug indomethacin. Melatonin (MLT) protection against indomethacin-induced oxidative tissue injury was investigated in gastric mucosa and testis of rats. MLT was administered intragastrically (i.g.) 30 min before the administration to fasted rats of 20 mg indomethacin/kg rat given i.g.. The area of gastric lesion as well as thiobarbituric acid reactive substances (TBARS) and lactate dehydrogenase (LDH) activity were found to be significantly increased 4 h after administration of indomethacin in rat gastric mucosa and testis indicating acute oxidative injury. MLT pretreatment reduced gastric lesion area to 80% of the indomethacin-treated rats and reduced the rise in TBARS concentration. MLT treatment reduced the LDH activity increase in testis but not in gastric mucosa. In indomethacin-treated rats, both the cytosolic Cu,Zn superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-SOD activities were significantly diminished in gastric mucosa as well as the total SOD activity in testis. In addition, glutathione (GSH) content in both tissues was markedly decreased following indomethacin treatment. Pretreatment with MLT significantly ameliorated both the inhibition of SOD activity and the decreased GSH content in both tissues. Thus, these results show the effective antiperoxidative and preventive actions of MLT against indomethacin-induced gastric mucosal damage and testicular oxidative injury and we propose that this action might be relevant for its use with other free radical generating drugs.