Abstract
Context A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by restraint stress, while melatonin (MT) elicits anti-inflammation and antioxidant effects. Objective The present study investigated the mechanisms of MT-mediated protection effects on restraint stress-induced GIMD. Materials and methods 144 8-week-old male ICR mice were divided into four groups: control, restraint stress, restraint stress + MT and MT (positive control). 20 mg/kg MT or vehicle were intraperitoneally injected 60 min before restraint stress (10 h/day) once daily for 3 days. Biochemical parameters, intestinal mucosal integrity, tissues antioxidant ability and autophagic proteins levels were determined. Results Mice subjected to restraint stress elevated NE level by 141.41% and decreased MT content by 38.82% in plasma. Consistent with the decrease in MT level, we observed a reduction in the antioxidant ability and an increase in autophagic proteins by 14.29–46.74% in the gut, resulting in injury to intestinal mucosa which was manifested by reductions in villus height and villus height/crypt depth (V/C) ratio, number of goblet and PCAN-positive cells, and expression of tight junction protein (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by restraint stress and improved the intestinal mucosal injury. However, there was no significant difference between MT (positive control) and control group. Discussion and conclusion Our results suggest that MT effectively mitigates psychological stress-induced injury to intestinal mucosa, providing evidence demonstrating the potential for using MT as therapy against intestinal impairment associated with psychological stress.
Highlights
IntroductionA growing body of evidence demonstrates that restraint stress damages the intestine and causes disorders such as inflammatory bowel disease (IBD) (Schultz et al 2015)
We found that restraint stress significantly increased plasma levels of NE and corticosterone, compared to the control group
This finding corroborates the results of past studies in which exposure of rats to 30 min of restraint stress increased hypothalamic NE concentration, while longer restraint was associated with an attenuation of NE upregulation (Keim and Sigg 1976)
Summary
A growing body of evidence demonstrates that restraint stress damages the intestine and causes disorders such as inflammatory bowel disease (IBD) (Schultz et al 2015). The pathogenesis underlying the induction of injury to intestinal mucosa by restraint stress remains controversial. A number of researchers have reported that gastrointestinal ulcerogenesis is caused by a deficiency in endogenous prostaglandin (PG), in intestinal ulcers resulting from the use of nonsteroidal antiinflammatory drugs (NSAID) (Adler et al 2009). Oxidative stress was shown to play a role in the pathogenesis of stressinduced gastric ulcers (Jia et al 2007). Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, thereby leading to excessive production of free radicals and resulting in irreversible cell damage (Mcintosh and Sapolsky 1996)
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