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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
 
BMC Gastroenterol. 2012; 12: 45.
Published online May 8, 2012. doi:  10.1186/1471-230X-12-45
PMCID: PMC3444430
High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity
Runkuan Yang,corresponding author1,2 Shutian Zhang,3 Antonella Cotoia,2 Niku Oksala,4 Shengtao Zhu,3 and Jyrki Tenhunen1,5
1Department of Intensive Care Medicine, University of Tampere Medical School, Tampere 33014, Finland
2Department of Critical Care Medicine, University of Pittsburgh Medical School, 3550 Terrace Street, Pittsburgh, PA 15261, USA
3Department of Gastroenterology, Friendship Hospital, Capital Medical School, Beijing, China
4Center of Laboratory Medicine, Tampere University Hospital and Surgery, University of Tampere Medical School, Tampere 33014, Finland
5Department of Surgical Sciences/Anaesthesiology and Intensive Care, University of Uppsala Medical School, Uppsala 75185, Sweden
corresponding authorCorresponding author.
Runkuan Yang: bobyangr/at/yahoo.com; Shutian Zhang: zhangst0612/at/sina.com; Antonella Cotoia: yuy22/at/pitt.edu; Niku Oksala: nikuoksala/at/gmail.com; Shengtao Zhu: shengtaozhu/at/126.com; Jyrki Tenhunen: jyrki.tenhunen/at/pshp.fi
Received November 17, 2011; Accepted May 8, 2012.
Abstract
Background
Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose.
Methods
Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses.
Results
24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration.
Conclusion
HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.
Articles from BMC Gastroenterology are provided here courtesy of
BioMed Central