Nesfatin-1 alleviates gastric damage via direct antioxidant mechanisms

Abstract Background Indomethacin is a nonsteroidal anti-inflammatory drug, which is known to produce serious side effects, causing ulcerative lesions. Nesfatin-1, a newly identified anorexigenic peptide, was recently shown to have neuroprotective effects. The aim of the study was to investigate the anti-inflammatory effects of nesfatin-1 on indomethacin-induced gastric ulcer. Materials and methods After a 24-h starvation period, ulcer was induced in Sprague–Dawley rats by subcutaneous administration of indomethacin (25 mg/kg), whereas control group received vehicle. Fifteen minutes after ulcer induction, rats were treated with either saline or nesfatin-1 (0.1, 0.3, or 1 μg/kg, intraperitoneally). At the fourth hour, all rats were decapitated and their trunk blood was collected for tumor necrosis factor (TNF)-α and interleukin (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. Results Ulcer induction increased serum TNF-α; and IL-6 levels, gastric CL and MDA levels and MPO activity but decreased gastric GSH content ( P P P Conclusions Nesfatin-1 alleviated indomethacin-induced gastric injury, suggesting that the anti-inflammatory and gastroprotective effects of nesfatin-1 on oxidative gastric damage could be implemented by supporting the balance in oxidant and antioxidant systems while inhibiting the generation of pro-inflammatory mediators.