Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2005; 11(27): 4154-4160
Published online Jul 21, 2005. doi: 10.3748/wjg.v11.i27.4154
Mechanisms of action of leptin in preventing gastric ulcer
Edward O. Adeyemi, Salim A. Bastaki, Irwin S. Chandranath, Mohammed Y. Hasan, Mohammed Fahim, Abdu Adem
Edward O. Adeyemi, Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Salim A. Bastaki, Irwin S. Chandranath, Mohammed Y. Hasan, Abdu Adem, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Mohammed Fahim, Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Author contributions: All authors contributed equally to the work.
Supported by the Faculty of Medicine and Health Sciences Research Grant, UAE University, United Arab Emirates
Correspondence to: Professor Abdu Adem, Department of Pharmacology, FMHS, UAE University, PO Box 17666, Al Ain, United Arab Emirates. abdu.adem@uaeu.ac.ae
Telephone: +971-3-7137522 Fax: +971-3-7672033
Received: October 23, 2004
Revised: January 10, 2005
Accepted: January 13, 2005
Published online: July 21, 2005
Abstract

AIM: To investigate the effects of leptin (1-20 μg/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 H2-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE2 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 H2-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 NG-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 PGE2 level in the gastric glandular tissues. Leptin also increased mucus secretion.

CONCLUSION: 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.

Keywords: Indomethacin; Acidified ethanol; Gastric ulcer; Prostaglandin; Ranitidine; Omeprazole; Lansoprazole; NG-nitro L-arginine methyl ester; Wistar rats