Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical.
The antiulcer effect of melatonin on gastric lesions caused by restraint-cold stress or by indomethacin (IMN) was studied with the intent of determining the mechanism of action of the indole. Melatonin dose-dependently prevents both stress and IMN-induced gastric damage with around 90% inhibition at a dose of 60 mg per kg BW. When compared with already-marketed antiulcer drugs, such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. When compared with other antioxidants, melatonin was more potent than glutathione and essentially equipotent to alpha-tocopherol in blocking stress-induced ulcer. As stress-induced gastric lesions are mainly caused by oxidative damage due to hydroxyl radicals (*OH), the effect of melatonin in scavenging the *OH generated during stress conditions, as well as in an in vitro model system, was studied. The results indicate that melatonin at the dose of 60 mg per kg BW caused an 88% reduction of endogenous *OH during stress. Melatonin was also highly effective in scavenging *OH generated in vitro by a Cu2+-ascorbate system. In this case, melatonin at 100 microM reduced *OH by 80%. Melatonin was also found to be a more potent radical scavenger than benzoate, a known *OH scavenger. The results indicate that melatonin prevents stress-induced gastric lesions by scavenging the endogenous *OH. As it also protects against IMN-induced gastric damage, it probably also offers gastroprotection by maintaining endogenous prostaglandin levels.
Bandyopadhyay
D
D
Department of Physiology, Indian Institute of Chemical Biology, Calcutta.
Biswas
K
K
Bandyopadhyay
U
U
Reiter
R J
RJ
Banerjee
R K
RK
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007213:Indomethacin; D015227:Lipid Peroxidation; D008550:Melatonin / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D010437:Peptic Ulcer / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000150:complications*
D000897:Anti-Ulcer Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D011899:Ranitidine; D008550:Melatonin; D009853:Omeprazole; D007213:Indomethacin