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dc.contributorInstituto Universitario de Biomedicina (IBIOMED)es_ES
dc.contributor.authorCrespo, Irene
dc.contributor.authorSan-Miguel, Beatriz
dc.contributor.authorSánchez, Diana I.
dc.contributor.authorGonzález-Fernández, Bárbara
dc.contributor.authorÁlvarez, Marcelino
dc.contributor.authorGonzález-Gallego, Javier
dc.contributor.authorTuñón González, María Jesús 
dc.contributor.otherOtroses_ES
dc.date2016-04-23
dc.date.accessioned2016-12-19T17:28:02Z
dc.date.available2016-12-19T17:28:02Z
dc.date.issued2016-12-19
dc.identifier.citationJournal of Pineal Research, 2016es_ES
dc.identifier.urihttp://hdl.handle.net/10612/5689
dc.description25 p.es_ES
dc.description.abstractThe sphingosine kinase (SphK)1/sphingosine-1-phosphate (S1P) pathway is involved in multiple biological processes, including liver diseases. This study investigate whether modulation of the SphK1/S1P system associates to the beneficial effects of melatonin in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2x104 hemagglutination units of a RHDV isolate and received 20 mg/kg of melatonin at 0 hr, 12 hr and 24 hr postinfection. Liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased in RHDV-infected rabbits. S1P production and protein expression of the S1PR1 receptor were significantly elevated following RHDV infection. These effects were significantly reduced by melatonin. Rabbits also exhibited increased expression of toll-like receptor (TLR)4, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, nuclear factor-kappa B (NF-κB) p50 and p65 subunits and phosphorylated inhibitor of kappa B (IκB)α. Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for RHDV viral VP60 antigen in the liver. Results obtained indicate that the SphK1/S1P system activates in parallel to viral replication and the inflammatory process induced by the virus. Inhibition of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in this animal model of ALF, and supports the potential of melatonin as an antiviral agentes_ES
dc.languageenges_ES
dc.publisherWileyes_ES
dc.subjectMedicina. Saludes_ES
dc.subject.otherLiveres_ES
dc.subject.otherSphingosine kinase 1es_ES
dc.subject.otherSphingosine-1-phosphatees_ES
dc.subject.otherAcute liver failurees_ES
dc.subject.otherMelatonines_ES
dc.titleMelatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origines_ES
dc.typeinfo:eu-repo/semantics/preprintes_ES


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