Melatonin modulates the effects of gastric injury in rats: role of prostaglandins and nitric oxide.
Experimental evidence has been presented connecting melatonin with the prevention or treatment of gastrointestinal disorders either by the scavenging properties of active oxygen or by receptor-mediated stimulation of gene expression of neutralizing enzymes. Prostaglandins and nitric oxide are important neuroimmunomodulators in digestive physiology and different studies have indicated that the protective properties of melatonin may be explained by prostaglandin and/or nitric oxide mechanisms. The aim of the present study was to examine the effect of intraperitoneal administration of melatonin on in vivo changes in PGE(2), generated in gastric mucosal lesions by ischemia-reperfusion. Cyclic GMP nucleotide was also studied as an index of the principal enzymatic activity involved in the metabolism of nitric oxide, the nitric oxide synthase. The different immunological tests showed that the intraperitoneal administration of melatonin prevents the postischemic decrease in prostaglandins. The concentration of this eicosanoid in the rat mucosa treated with 20 mg.kg(-1) of melatonin was significantly higher (p < 0.05) than that in the control rats. The amount of cyclic GMP in the stomach decreased because of ischemia-reperfusion. In treated animals however, a marked increase occurred in concentrations of GMP, but the difference was not statistically significant. The results suggest that the mechanism of protection afforded by melatonin against lesions induced by gastric ischemia-reperfusion may be due to stimulation of the synthesis of eicosanoid protectors during the ischemic process.
Cabeza
Juan
J
Departamento de Farmacología, Facultad de Farmacia, Sevilla, Spain.
Alarcón-de-la-Lastra
Catalina
C
Jiménez
Dolores
D
Martín
María-José
MJ
Motilva
Virginia
V
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013272:Stomach Diseases / Q000188:drug therapy* / Q000378:metabolism
D000975:Antioxidants; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP; D008550:Melatonin; D015232:Dinoprostone