Mechanisms involved in gastric protection of melatonin against oxidant stress by ischemia-reperfusion in rats.
The generation of oxygen-derived free radicals has been suggested to be significantly responsible for ischemia-reperfusion injury in gastrointestinal tissues. Biochemical mechanisms include the xanthine-oxidase-derived oxidants mainly the superoxide anion. Both in vitro and in vivo studies have demonstrated that the pineal hormone melatonin possesses free radical scavenging and antioxidant properties. The indolamine has been effective in reducing the induced-oxidative damage in several tissues and biological systems. The aim of this study was to elucidate additional antioxidant mechanisms responsible for the gastroprotection afforded by the indolamine in ischemia-reperfusion gastric injury. Therefore, changes of related enzymes such as xanthine-oxidase, superoxide dismutase, glutathione reductase and total glutathione were investigated. Our results showed that treatment with 5, 10 or 20 mg kg(-1) of melatonin, administered i.p., clearly diminished the percentage of damage to 49.56 +/- 17.20, 37.54 +/- 11.40 and 26.70 +/- 8.12 respectively. Histologically there was a reduction of exfoliation of superficial cells and blood cell infiltration. These protective effects were related to a significant reduction of xanthine-oxidase activity (2.23 +/- 0.38 U/mg prot x 10(-4) with the highest tested dose of melatonin) and significant increases in superoxide dismutase reaching a value of 6.20 +/- 0.56 U/mg prot with 25 mg/Kg of melatonin and glutation reductase activities (417.44 +/- 29.72 and 649.43 +/- 81.11 nmol/min/mg prot with 10 and 20 mg/Kg of melatonin). We conclude that the free radical scavenger properties of melatonin mainly of the superoxide anion, probably derived via the xanthine-oxidase pathway, and the increase of antioxidative enzymes significantly contributes to mediating the protection by the hormone against ischemia-reperfusion gastric injury.
Cabeza
J
J
Departamento de Farmacología, Facultad de Farmacia, Sevilla, Spain.
Motilva
V
V
Martín
M J
MJ
de la Lastra
C A
CA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005980:Glutathione Reductase; D005978:Glutathione; D008550:Melatonin