Mechanisms of action of leptin in preventing gastric ulcer.
OBJECTIVE
To investigate the effects of leptin (1-20 microg/kg) on acidified ethanol (AE)- and indomethacin (Indo)-induced gastric lesions in rats and compare it with ranitidine, lanso-prazole, and omeprazole and to determine its mechanisms of actions.


METHODS
Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors (PPIs) lansoprazole and omeprazole, or H(2)-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE(2) concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content.


RESULTS
Subcutaneous administration of leptin, two PPIs lansoprazole and omeprazole or H(2)-receptor antagonist ranitidine 30 min before AE or Indo produced a dose-dependent and reproducible inhibition of gastric ulcers (GUs). This inhibition was found to be more potent than other antagonists used. In N(G)-nitro L-arginine methyl ester (L-NAME)-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced, compared to rats without L-NAME pretreatment. However, the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE(2) level in the gastric glandular tissues. Leptin also increased mucus secretion.


CONCLUSIONS
The results of the present study show that leptin inhibits GU formation by AE or Indo in a dose-dependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.
Adeyemi
Edward O
EO
Department of Internal Medicine, UAE University, Al Ain, United Arab Emirates.
Bastaki
Salim A
SA
Chandranath
Irwin S
IS
Hasan
Mohammed Y
MY
Fahim
Mohammed
M
Adem
Abdu
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D064747:Lansoprazole; D020738:Leptin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D020738:Leptin; D064747:Lansoprazole; D009569:Nitric Oxide; D011899:Ranitidine; D011451:Prostaglandin-Endoperoxide Synthases; D009853:Omeprazole