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RETRACTED: Melatonin attenuates apoptotic liver damage in fulminant hepatic failure induced by the rabbit hemorrhagic disease virus
Author(s) -
Tuñón María J.,
Miguel Beatriz San,
Crespo Irene,
Jorquera Francisco,
Santamaría Eva,
Alvarez Marcelino,
Prieto Jesús,
GonzálezGallego Javier
Publication year - 2011
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.2010.00807.x
Subject(s) - melatonin , apoptosis , biology , endocrinology , medicine , fas ligand , caspase 3 , programmed cell death , biochemistry
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.