Objective To investigate the effects of melatonin (MT) on intestinal mucosal injury associated with intermittent hypoxic (HI) in rats. Methods Thirty-six male Wistar rats were randomly divided into control (Ctrl), HI, MT groups (n = 12 per group). Each group was further divided into 2- and 4-week subgroups (n = 6 per group per time point), with different animals used at the two terminal sampling time points. Rats in the Ctrl group were exposed to compressed air, whereas rats in the HI and MT groups underwent intermittent hypoxia for 7 h daily. MT (20 mg/kg) was administered intraperitoneally before each daily exposure, while rats in the Ctrl and HI groups received an equivalent volume of vehicle. At the designated 2- or 4-week endpoint, the sampling procedure was initiated immediately after completion of the final daily exposure. Small intestinal tissue and central venous blood were collected. Intestinal histopathological changes were assessed by hematoxylin and eosin staining and Chiu scoring, and villus area, height, thickness, and crypt depth were measured. Serum ROS, MDA, SOD, and DAO levels were determined. Result Intermittent hypoxia was associated with intestinal histopathological injury and significant reductions in villus area, villus height, villus thickness, and crypt depth at both 2 and 4 weeks. At 2 weeks, no significant differences in villus morphometric parameters were observed between the MT and HI groups, at 4 weeks, villus area and height were significantly greater in the MT group than in the HI group. At 2 weeks, SOD activity was significantly higher in the MT group than in the HI group, whereas ROS, MDA, and DAO levels did not differ significantly between these groups. At 4 weeks, the MT group showed significantly lower ROS, MDA, and DAO levels and significantly higher SOD activity than the HI group. Histological findings also indicated less severe intestinal mucosal injury in MT-treated rats. Conclusion Intermittent hypoxia was associated with intestinal mucosal injury and changes in oxidative stress-related biochemical indicators in rats. Melatonin treatment was associated with attenuation of histopathological injury and a more favorable biochemical profile, with these differences being more evident at 4 weeks.
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