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

Abstract

AimsNeuropeptide 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 methodsSprague-Dawley rats were subjected to WIRS for 6 h, and treated with NPW (0.1, 0.3, 1 and 5 μg/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 findingsNPW 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-α 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. SignificanceOur 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.