| Melatonin attenuates apoptotic liver damage in fulminant hepatic failure induced by the rabbit hemorrhagic disease virus. | |
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MedLine Citation:
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PMID: 20964705 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Hepatocyte apoptosis plays an important role in the development of fulminant hepatic failure (FHF). The objective of this study was to investigate the antiapoptotic effect of melatonin in an animal model of FHF of viral origin induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received melatonin at two concentrations of 10 and 20 mg/kg at 0, 12, and 24 hr postinfection. RHDV infection induced liver apoptosis, with increased caspase-3 immunoexpression and activity and poly(ADP-ribose)polymerase-1 (PARP-1) proteolysis. These effects were attenuated by melatonin in a concentration-dependent manner. Antia-poptotic effects of melatonin were related to a reduced expression of Bax and cytosolic cytochrome c release, increased expression of Bcl-2 and Bcl-xL, and inhibition of caspase-9 activity. Increased thiobarbituric reactive acid substances concentration and oxidized-to-reduced glutathione ratio were significantly prevented by melatonin administration. Melatonin treatment also resulted in a reduction in caspase-8 activity, tumor necrosis factor receptor-1 (TNF-R1) expression, and phosphorylated Janus kinase (JNK) expression, and increased expression of cellular FLICE-inhibitory protein (c-FLIP). Our findings show that inhibition of apoptotic mechanisms contributes to the beneficial effects of melatonin in rabbits with experimental infection by RHDV and supports a potential hepatoprotective role of melatonin in FHF. |
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Authors:
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María J Tuñón; Beatriz San Miguel; Irene Crespo; Francisco Jorquera; Eva Santamaría; Marcelino Alvarez; Jesús Prieto; Javier González-Gallego |
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Publication Detail:
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Type: Journal Article Date: 2010-10-22 |
Journal Detail:
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Title: Journal of pineal research Volume: 50 ISSN: 1600-079X ISO Abbreviation: J. Pineal Res. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 38-45 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S. |
Affiliation:
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Institute of Biomedicine (IBIOMED), University of León, León, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Unit, Hospital of León, León, Spain Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain Department of Animal Health, University of León, León, Spain. |
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