Peripheral administration of Neuropeptide-W protects against stress-induced gastric injury in rats

Abstract

Aims: Neuropeptide W (NPW) participates in the regulation of neuroendocrine response to stress, but the possible protective effects of NPW against stress-induced gastric ulcers have not yet been evaluated. The purpose of the present study was to investigate whether peripherally administered NPW could have gastroprotective effects in water-immersion restraint stress (WIRS)-induced gastric injury.Main methods: Sprague-Dawley rats were subjected to WIRS for 6 h, and treated with NPW (0.1, 0.3, 1 and 5 mu g/ kg) or saline at 30 min before WIRS application. Under anesthesia, capsaicin (1 %) was applied perivagally for degeneration of vagal afferent fibers (VAD) at two weeks before WIRS protocol. Blood, gastric and brain tissues were obtained for biochemical, molecular and histological assessments.Key findings: NPW treatment given immediately before WIRS application attenuated stress-induced gastric oxidant damage along with an increase in gastric blood flow, while similar gastroprotective effects were observed in NPW-treated rats with denervated vagal afferents. NPW prevented elevations in serum IL-6 and TNF-alpha levels, and increased cycloxygenase-1 mRNA, but suppressed cycloxygenase-2 mRNA levels. In addition, WIRS-induced downregulation of NPW expression in the brain tissue was reversed in NPW-treated rats having less severe ulcers, suggesting that cerebral NPW production could be critical in the central regulation of stress-induced ulcerogenesis.Significance: Our results demonstrate for the first time that the peripheral administration of NPW offers an anti-ulcer activity in stress-induced gastric ulcer by regulating gastric blood flow, suppressing oxidant damage and inflammation via the modulation of COX-induced gastroprotection and without the contribution of vagal afferent fibers.