Anti-inflammatory effects of nesfatin-1 on acetic acid-induced gastric ulcer in rats: Involvement of Cyclo-oxygenase pathway

In order to elucidate the contribution of cycloxygenase (cox) enzymes in the anti-oxidant and anti-inflammatory mechanisms of nesfatin-1,which improves the healing process of chronic gastric ulcers,either acetic acid (80%; ulcer groups; n = 40) or saline (control groups; n = 40) was applied to the serosal surface of male sprague dawley rats’ stomachs for 1 min. both the control and ulcer groups were treated daily with either i.p. saline or nesfatin-1 (0.3 µg/kg; for 3 days). nesfatin-1-treatment was preceded with i.p. saline,cox-2 inhibitor ns-398 (2 mg/kg),cox-1 inhibitor ketorolac (3 mg/kg) or non-selective cox inhibitor indomethacin (5 mg/kg) for 3 days. the rats were decapitated at the end of the third day,and their trunk blood was collected for the measurements of tumor necrosis factor-α (tnf-α),interleukin-1β (il-1β) and il-10 using elisa. the induction of ulcers resulted in increased macroscopic scores,along with elevated gastric malondialdehyde,luminol- and lucigenin-enhanced chemiluminescence levels and myeloperoxidase activity. on the other hand,nesfatin-1 treatment abolished these elevations. depleted glutathione,superoxide dismutase and catalase activity levels in the saline-treated ulcer group were preserved in the nesfatin-1-treated ulcer group. increased levels of serum tnf-α,il-1β,il-10 in the saline-treated ulcer group,as compared to control group,were significantly decreased in the nesfatin-1-treated ulcer group. the inhibition of cox-1,and/or cox-2 reversed most of the alterations induced with nesfatin-1,but cox-2-blockade was consistently more effective to abolish all nesfatin-1-induced changes. our results suggest that nesfatin-1 ameliorates ulcer-induced inflammatory response through the modulation of oxidant-antioxidant balance. as selective pharmacological inhibition of cox-1 or cox-2 suppresses the antioxidant/anti-inflammatory effects of nesfatin-1,it appears that nesfatin-1 decreases inflammatory mediators and neutrophil migration by a cox-dependent mechanism,especially by a cox-2- dependent mechanism,during the ulcer healing stage. © 2017,polish physiological society. all rights reserved.