Nesfatin-1 treatment alleviates indomethacin-induced gastric ulcer in rats

Background: Indomethacin is a non-steroidal anti-inflammatory drug, which is known to produce serious adverse effects, including ulcerative lesions. Nesfatin-1, a newly identified anorexigenic peptide, was recently shown to have antioxidant effects. Aim: This study aimed to investigate the possible ameliorative effect of nesfatin-1 against indomethacin induced gastric ulcer in rats, with exploration of the possible mechanisms underlying this effect. Design: 24 adult male albino rats were used. Ulcers were induced using oral indomethacin (20mg/kg) daily for 7 days. The rats were randomly assigned to vehicle treated control group(I), indomethacin treated (II), and indomethacin treated for 7 days followed by nesfatin-1 (1ug/kg i.p) daily for 10 days. Assessment of gastric juice parameters (total acid output, pepsin activity and mucin content), gastric mucosal levels of malondialdehyde (MDA) , tumor necrosis factor –alpha (TNF-alpha) , nitrite and prostaglandin E2 (PGE2) levels were also determined, in addition to the histopathologic examination of the gastric mucosa in each group. Results: Nesfatin-1 displayed a significant ameliorative effect in gastric lesions induced by indomethacin as indicated by the histopathology and reduction in measured gastric juice parameters (P<0.001). It also reduced both gastric mucosal MDA and TNF-alpha significantly (P< 0.001) and increased nitrite and PGE2 levels in this ulcer model (P< 0.001). Conclusion: Nesfatin-1 attenuates indomethacin induced gastric ulcer and potentiates ulcer healing in the stomach of rats exposed to chronic administration of indomethacin, this effect depend upon decrease in gastric secretion, increase in nitric oxide and PGE2, besides antioxidant and anti-inflammatory roles.