Abstract
Aim:
This study investigated the effect of intragastrically administered melatonin on intestinal mucosal permeability induced by diclofenac in mice.
Methods:
Intestinal mucosal permeability was induced in mice by intragastric administration of diclofenac (2.5 mg/kg). Melatonin was given intragastrically (10 mg/kg) once per day for 3 d after diclofenac administration. The small intestine was examined macroscopically and microscopically for pathologic injury to the intestinal mucosa. Intestinal mucosal permeability was evaluated by Evans blue and FITC-dextran methods. Mitochondrial functional parameters, including mitochondrial membrane potential, mitochondrial ATPase and succinate dehydrogenase (SDH) activity, were assessed. The malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined from small intestinal mucosal homogenates.
Results:
As compared with control mice, the permeability, pathologic score, MDA and MPO levels and ulceration of the intestinal mucosa were increased significantly by diclofenac treatment, and a broadened junctional complex and enlarged intercellular space were observed by transmission electron microscopy (TEM). Melatonin treatment significantly reduced the intestinal mucosal permeability, pathologic score, MDA, and MPO levels and ulceration of the intestinal mucosa. By TEM, the small intestine villus morphology and intercellular spaces were nearly normal in melatonin-treated mice. At the level of the mitochondria, melatonin treatment significantly restored the activities of ATPase and SDH.
Conclusion:
The intestinal damage and increased intestinal permeability induced by diclofenac in mice was limited by melatonin; moreover, melatonin preserved several aspects of mitochondrial function.
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Mei, Q., Diao, L., Xu, Jm. et al. A protective effect of melatonin on intestinal permeability is induced by diclofenac via regulation of mitochondrial function in mice. Acta Pharmacol Sin 32, 495–502 (2011). https://doi.org/10.1038/aps.2010.225
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DOI: https://doi.org/10.1038/aps.2010.225
