Effect of Leptin on Cold Restraint-Induced Gastric Lesions in Albino Rats

Leptin, 167 amino acid peptide hormone, is secreted by adipocytes, has been found to
be present in the gastric mucosa. The locally secreted leptin was proved to have a
cytoprotective effect. To investigate whether exogenous leptin may be implicated in
gastric mucosal protection, male albino rats were randomly assigned to six groups of
six rats each. The rats of control (C) group were left freely wandering in their cages.
The rats of cold restraint stress (CRS) group were exposed to cold restraint stress for
three hours. The rats of leptin (L) group were given leptin subcutaneously (SC) in a
dose of 10 g/kg/rat 30 minutes before subjection to CRS. The rats of famotidine (F)
group were given famotidine SC in a dose of 50 mg/kg/rat just before subjection to
CRS. The rats of L-NAME group were injected with N
G
-nitro-L-arginine methyl ester
in a dose of 25 mg/kg/rat SC 15 minutes before giving leptin and 45 minutes before
being exposed to CRS. The rats of indomethacin (I) group were injected with
indomethacin SC in a dose of 10 mg/kg/rat followed 30 minutes later by leptin (10
g/kg/rat, SC) and exposure to CRS. Pyloric ligation was done in all animals at the
beginning of the experiment to collect the gastric juice for analysis. The juice was
analysed to determine its volume, pH, free and total acid concentration (FAC and
TAC), proteolytic activity and mucin concentration. Lesions of gastric mucosa were
scored, the ulcer index (UI) and preventive index (PI) were calculated. Gastric
mucosa was scrapped and stored at –80
o
C until used for assay of gastric mucosal
prostaglandin E2(PGE2). Exposure to CRS significantly reduced gastric juice
volume, pH and mucin concentration and gastric mucosal PGE2and significantly
increased gastric juice proteolytic activity and acidity (FAC and TAC) in CRS group
compared with C group. CRS induced ulcerative lesions in all rats achieving an UI of
19.25. Administration of leptin or famotidine before exposure to CRS significantly
increased gastric juice volume, pH and mucin concentration and gastric mucosal
PGE2 and significantly decreased gastric juice proteolytic activity in L and F groups
compared with CRS group. Both leptin and famotidine exhibited profound protection
of gastric mucosa against CRS-induced lesions achieving an UI of 9.5 and 9.75 in L
and F groups respectively. This was evident from the PI which was 50.65 and 49.35
in L and F groups respectively. Administration of L-NAME or indomethacin before
exposure to CRS aggravated CRS-induced gastric mucosal lesion achieving an UI of
10.75 and 14 in L-NAME and I groups respectively. It could be concluded from the
present study that exogenous leptin has an ulcer preventing ability in case of CRS
which is comparable to that of famotidine, the famous H2antagonist. The mechanism of ulcer prevention of leptin may involve the cyclooxygenase and nitric oxide pathways. These results may have consequence for the clinical practice.