Melatonin protects against piroxicam-induced gastric ulceration

Abstract

The antiulcer effect of melatonin on gastric lesions caused by piroxicam was studied with the intent of determining the mechanism of action of this agent. Melatonin dose-dependently lowered piroxicam and indomethacin-induced gastric damage with more than 90% inhibition at a dose of 60 mg/kg BW. Increased lipid peroxidation, augmented protein oxidation and decreased glutathione content of the gastric tissue following piroxicam treatment indicated a possible involvement of oxidative stress in this nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Pretreatment of rats with melatonin prevented these changes. Oral administration of piroxicam to rats caused a threefold increase in the tissue levels of hydroxyl radical generation, a change significantly attenuated by melatonin. Furthermore, a decrease in the activity of gastric peroxidase and an increase in the activity of gastric superoxide dismutase(s) (SOD) because of piroxicam treatment was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. The results of the present studies also reveal that melatonin may influence the expression of Cu-Zn SOD, catalase, cyclooxygenase as well as alpha-actinin whose levels were found to be altered, following piroxicam treatment. The current studies, therefore, document melatonin's gastroprotective ability against piroxicam-induced gastric damage and the findings raise the possibility of melatonin being considered as a co-therapy with piroxicam or other NSAIDs in reducing the gastropathy when long-term use of these nonsteroidal agents are unavoidable.