Abstract

Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients. 3,4-Methylenedioxyphenol (sesamol) has been reported to have potent antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of sesamol on water immersion restraint- (WIR-) induced SRMD in rats. Rat gastric ulcer and hemorrhage were induced by WIR. Rats were pretreated orally with various doses of sesamol (0.1, 0.3, and 1 mg/kg, resp.) 30 min before WIR. Gastric mucosal ulceration, hemoglobin, lipid peroxidation, mucus secretion, proinflammatory cytokines, and nuclear factor (NF)-κB levels were determined 4 h after WIR. In addition, the infiltration of neutrophil and macrophage into gastric mucosa was also determined after WIR. Water immersion restraint increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels but failed to affect mucosal lipid peroxidation and mucus secretion compared with non-WIR. Sesamol significantly decreased gastric ulceration and hemorrhage and inhibited mucosal TNF-α, IL-1β, and IL-6 production and NF-κB activity in WIR-treated rats. In addition, increased myeloperoxidase and CD68 levels in gastric mucosa were found in WIR-treated rats compared to non-WIR rats. Sesamol did not affect myeloperoxidase but decreased CD68 levels in mucosa in WIR-treated rats. Sesamol may protect against SRMD by inhibiting gastric mucosal proinflammatory cytokines in rats.

Highlights

  • Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients [1]

  • Water immersion restraint (WIR) group increased ulcer index and luminal hemoglobin levels compared with non-WIR group, while sesamol decreased both indicators compared to WIR group rats (Figures 1(a) and 1(b))

  • We used morphological and histological studies to further confirm the protective effect of sesamol on stress-induced gastric mucosal injury

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Summary

Introduction

Stress-related mucosal disease (SRMD) (i.e., gastric mucosal damage, ulceration, and bleeding) causes considerable morbidity and mortality in critically ill patients [1]. The mortality rate from stressrelated mucosal bleeding is nearly 50% [2]. Antacids such as histamine H2 receptor antagonist and proton pump inhibitor have been used to treat patients with stress ulcer; they have been suggested to be associated with the incidence of nosocomial pneumonia and the inhibition of immune function [3,4,5]. Water immersion restraint (WIR), a model that mimics the clinical acute gastric hemorrhage and ulceration, has been widely accepted for studying stress-related gastric mucosal injury [6, 7]. Gastric mucosal inflammation is important in stressassociated gastric mucosal damage [11, 12]

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