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Long‐term oral melatonin administration reduces ethanol‐induced increases in duodenal mucosal permeability and motility in rats
Author(s) -
Sommansson A.,
Yamskova O.,
Schiöth H. B.,
Nylander O.,
Sjöblom M.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12339
Subject(s) - motility , melatonin , intestinal permeability , ethanol , chemistry , pharmacology , term (time) , medicine , microbiology and biotechnology , biology , biochemistry , physics , quantum mechanics
Aim Increased intestinal epithelial permeability is associated with intestinal inflammation and dysfunction. The aim of the present study was to investigate the role of long‐term oral melatonin administration on ethanol‐induced increases in duodenal mucosal permeability and hypermotility. Methods Male Sprague‐Dawley rats were administered melatonin in their tap water (0.1 mg mL −1 or 0.5 mg mL −1 ) for 2 or 4 weeks. After the treatment period, the rats were anaesthetized with Inactin ® , and a 30‐mm duodenal segment was perfused in situ . The effects on duodenal mucosal paracellular permeability, bicarbonate secretion, fluid flux and motor activity were studied. The expression levels of the tight junction components, zona occludens (ZO)‐1, ZO‐2, and ZO‐3, claudin‐2, claudin‐3, claudin‐4, occludin, and myosin light chain kinase and of the melatonin receptors MT 1 and MT 2 were assessed using qRT ‐PCR. Results Melatonin administration for 2 weeks significantly reduced the basal paracellular permeability, an effect that was absent after 4 weeks. Perfusing the duodenal segment with 15% ethanol induced marked increases in duodenal paracellular permeability, bicarbonate secretion and motor activity. Melatonin for 2 weeks dose‐dependently reduced ethanol‐induced increases in permeability and motor activity. Four weeks of melatonin administration reduced the ethanol‐induced increases in duodenal motility and bicarbonate secretion but had no effect on the increases in permeability. Two weeks of melatonin administration upregulated the expression of MT 1 and MT 2 , although both were downregulated after 4 weeks. Melatonin downregulated the expression of ZO‐3 and upregulated the expression of claudin‐2, even as all other mRNA ‐levels investigated were unaffected. Conclusion Although further studies are needed, our data demonstrate that melatonin administration markedly improves duodenal barrier functions, suggesting its utility in clinical applications when intestinal barrier functions are compromised.