Role of melatonin in intestinal mucosal injury induced by restraint stress in mice

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.