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RETRACTED: Melatonin attenuates inflammation and promotes regeneration in rabbits with fulminant hepatitis of viral origin
Author(s) -
Laliena Almudena,
Miguel Beatriz San,
Crespo Irene,
Alvarez Marcelino,
GonzálezGallego Javier,
Tuñón María J.
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2012.00995.x
Subject(s) - melatonin , endocrinology , medicine , biology , stat protein , epidermal growth factor , luzindole , growth factor , mapk/erk pathway , tumor necrosis factor alpha , fas ligand , signal transduction , immunology , stat3 , receptor , melatonin receptor , apoptosis , microbiology and biotechnology , programmed cell death , biochemistry
The objective of the present study was to investigate the effect of melatonin on the liver inflammatory and regenerative response in an animal model of fulminant hepatic failure (FHF) of viral origin. Rabbits were experimentally infected with 2 × 10 4 hemagglutination units of a rabbit hemorrhagic disease virus (RHDV) isolate and received melatonin at two concentrations of 10 or 20 mg/kg at 0, 12 and 24 hr postinfection. RHDV infection induced an inflammatory response, with increased expression of toll‐like receptor 4, high‐mobility group box (HMGB)1, interleukin (IL)‐1β, IL‐6, tumor necrosis factor‐α, and C‐reactive protein, and decreased expression of decay accelerating factor (DAF/CD55). These effects were significantly reduced by melatonin. Matrix metalloproteinase‐9 expression was also lowered in melatonin‐treated rabbits. RHDV infection inhibited the hepatic regenerative/proliferative response, with a reduced expression of hepatocyte growth factor (HGF), epidermal growth factor, platelet‐derived growth factor (PDGF)‐B and vascular endothelial growth factor and their receptors; these responses were prevented by melatonin administration. Melatonin treatment also resulted in reduced expression of phosphorylated Janus kinase and enhanced expression of extracellular mitogen‐activated protein kinase (ERK) and signal transducer and activator of transcription (STAT) 3. Our findings show that anti‐inflammatory effects and stimulation of regenerative mechanisms contribute to the beneficial effects of melatonin in rabbits with experimental infection by RHDV and support a potential hepatoprotective role of melatonin in FHF.