Neuropeptide W Facilitates Chronic Gastric Ulcer Healing by the Regulation of Cyclooxygenase and NF-κB Signaling Pathways

Abstract

Abstract Putative beneficial effects of NPW in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. In anesthetized male Sprague-Dawley rats, acetic acid was applied surgically on the serosa and then a COX inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. At 1-h of ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 µg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX inhibitors, omeprazole or saline were continued for the following 2 days until they were decapitated at the end of the third day. NPW treatment depressed the gastric PGI2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced the gastric and serum TNF-α and IL-1β levels and depressed the upregulation of NF-κB and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.