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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 (<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>) induced by the rabbit hemorrhagic disease virus (<jats:styled-content style=\"fixed-case\">RHDV<\/jats:styled-content>). Rabbits were experimentally infected with 2\u00a0\u00d7\u00a010<jats:sup>4<\/jats:sup> hemagglutination units of a <jats:styled-content style=\"fixed-case\">RHDV<\/jats:styled-content> isolate and received 20\u00a0mg\/kg of melatonin at 0, 12, and 24\u00a0hr postinfection. Liver <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels, protein concentration, and immunohistochemical labeling for SphK1 increased in <jats:styled-content style=\"fixed-case\">RHDV<\/jats:styled-content>\u2010infected rabbits. S1P production and protein expression of the S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>1 receptor were significantly elevated following <jats:styled-content style=\"fixed-case\">RHDV<\/jats:styled-content> infection. These effects were significantly reduced by melatonin. Rabbits also exhibited increased expression of toll\u2010like receptor (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>)4, tumor necrosis factor alpha (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>), interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20106, nuclear factor\u2010kappa B (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B) p50 and p65 subunits, and phosphorylated inhibitor of kappa B (I<jats:italic>\u03ba<\/jats:italic>B)<jats:italic>\u03b1<\/jats:italic>. Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for <jats:styled-content style=\"fixed-case\">RHDV<\/jats:styled-content> viral <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>60 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 <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>, and supports the potential of melatonin as an antiviral agent.<\/jats:p>","DOI":"10.1111\/jpi.12335","type":"journal-article","created":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T19:45:39Z","timestamp":1461354339000},"page":"168-176","source":"Crossref","is-referenced-by-count":32,"title":["RETRACTED: Melatonin inhibits the sphingosine kinase 1\/sphingosine\u20101\u2010phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin"],"prefix":"10.1111","volume":"61","author":[{"given":"Irene","family":"Crespo","sequence":"first","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelino","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Animal Health University of Le\u00f3n Le\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gonz\u00e1lez\u2010Gallego","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Le\u00f3n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Tu\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED) University of Le\u00f3n Le\u00f3n Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Le\u00f3n 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