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

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.

Keywords

• gut
• tight junction protein
• antioxidant ability
• autophagy
• oxidative stress