A protective effect of melatonin on intestinal permeability is induced by diclofenac via regulation of mitochondrial function in mice

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.

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

“…This is supported by a recent study in which melatonin ameliorated diclofenac-induced increases in small intestinal permeability by restoring the tight junction structure (22). In addition, melatonin has been shown to ameliorate radiotherapy-induced intestinal damage (23,33), protect against postburn gut inflammation (4), and reduce bacterial translocation in colitis and after ischemiareperfusion injury (1,26,42,50).…”

Melatonin ameliorates Aβ1-42-induced Alzheimer's cognitive deficits in mouse model

“…In the second step, we use JC-1 to assess the inhibition of mitochondrial damage induced by melatonin in AD models. The beneficial effects of melatonin on mitochondrial function in neurons were documented by the following results, [41,46] and melatonin pretreatment prevented the raise of mitochondrial membrane potential (ΔΨm). At the high level of mitochondrial membrane potential (ΔΨm), JC-1 tended to form polymer and generate red fluorescence.…”

Study of Melatonin as Preventive Agent of Gastrointestinal Damage Induced by Sodium Diclofenac

“…When comparing with other NSAIDs, such as acetylsalicylic acid (ASA) whose pKa is 3.5, an almost four times higher concentration of ASA is necessary to produce the same effect as SD. Furthermore, other authors studied the role of MLT to recover intestinal permeability after a SD treatment [53], so SD is a proper model of GI injury.…”