Objectives: 

It is well documented that non-steroidal anti-inflammatory drugs, e.g. indomethacin, may cause gastric ulcer, characterized by disruption of mucosal integrity with the involvement of activated pro-inflammatory cytokines. Nesfatin-1, a newly identified anorexigenic peptide expressed in several organs including stomach, was recently shown to have neuroprotective effects. The aim was to investigate the anti-inflammatory effects of nesfatin-1 on indomethacin-induced gastric ulcer.

Materials: 

Following a 24-h starvation period, ulcer was induced in Sprague-Dawley rats (250-300g) by subcutaneous administration of indomethacin (25mg/kg), while control group received vehicle (5% NaHCO3). Fifteen minutes after ulcer induction, rats were treated with either saline or nesfatin-1 (0.1, 0.3 or 1 mg/kg, intraperitoneally). At the 4th hour, all rats were decapitated, and their trunk blood was collected for TNF-alpha; and IL-6 measurements. Stomach samples were examined microscopically, and analyzed for myeloperoxidase(MPO)activity, malondialdehyde(MDA), glutathione (GSH), luminol and lucigenin-enhanced chemiluminescence (CL) levels. Mann-Whitney U and Student's t-test were used for statistical analyses. Values of p<0.05 was regarded as significant.

Results: 

Ulcer induction increased serum TNF-alpha; and IL-6 levels, gastric CL and MDA levels and MPO activity, but decreased gastric GSH content (p<0.05-0.001). On the other hand, 0.1mg/kg dose of nesfatin-1 reduced microscopic and macroscopic damage scores, decreased MPO activity and MDA levels, CL and IL-6 levels, while gastric GSH was replenished(p<0.01). However, indomethacin-induced increase in TNF-&#945; level was abolished at only the 1 mg/kg dose of nesfatin-1 (p<0.01).

Conclusions: 

Results demonstrate that nesfatin-1 exerts antiulcerogenic effects by inhibiting gastric neutrophil infiltration, suppressing the release of pro-inflammatory cytokines and free radicals. Further experiments are required to elucidate the potential therapeutic action of nesfatin-1 in improving oxidative gastric injury.