Prolonged Administration of Melatonin Ameliorates Liver Phenotypes in Cholestatic Murine Model

• DOI: 10.1016/j.jcmgh.2022.07.007
• Publication Date: 2022-07-19T02:41:58Z
• Authors: Ludovica Ceci; Lixian Chen; Leonardo Baiocchi; Nan Wu; Lindsey Kennedy; Guido Carpino; Konstantina Kyritsi; Tianhao Zhou; Travis Owen; Debjyoti Kundu; Amelia Sybenga; Abdulkadir Isidan; Burcin Ekser; Antonio Franchitto; Paolo Onori; Eugenio Gaudio; Romina Mancinelli; Heather Francis; Gianfranco Alpini; Shannon Glaser
• Keywords: Liver Cirrhosis; Male; 0301 basic medicine; Settore MED/12 - GASTROENTEROLOGIA; Cholangitis, Sclerosing; Receptors, Melatonin; 610; Mice; 03 medical and health sciences; Transferases; TGF-β1; 616; Animals; Humans; cholangiopathies; circadian rhythm; ductular reaction; TGFβ1; Original Research; Melatonin; Cholestasis; Ductular Reaction; Circadian rhythm; Drinking Water; TGFβ1; Ductular reaction; Glutathione; Circadian Rhythm; Rats; 3. Good health; Disease Models, Animal; Phenotype; Settore MEDS-10/A - Gastroenterologia; Cholangiopathies

Primary sclerosing cholangitis (PSC) is characterized by biliary senescence and hepatic fibrosis. Melatonin exerts its effects interacting with receptor 1 2 (MT1/MT2) melatonin receptors. Short-term (1 wk) treatment reduces a ductular reaction liver fibrosis in bile duct-ligated rats down-regulation of MT1 clock genes, multidrug resistance gene knockout (Mdr2-/-) mice decreased miR200b-dependent angiogenesis. We aimed to evaluate the long-term on phenotype that may be mediated changes MT1/clock genes/miR200b/maspin/glutathione-S transferase (GST) signaling.Male wild-type Mdr2-/- had access drinking water with/without for 3 months. Liver damage, proliferation/senescence, fibrosis, peribiliary inflammation, angiogenesis were measured staining sections, quantitative polymerase chain enzyme-linked immunosorbent assay samples. confirmed link between genes/miR200b/maspin/GST/angiogenesis signaling Ingenuity Pathway Analysis software phenotypes aforementioned pathway samples from mouse groups, healthy controls, PSC patients immortalized human cholangiocytes.Chronic administration ameliorates phenotypes, which associated expression.Melatonin improves histology restores circadian rhythm interaction through increased maspin/GST activity.