High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity

Yang, R and Zhang, S and Cotoia, A and Oksala, N and Zhu, S and Tenhunen, J (2012) High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity. BMC Gastroenterology, 12.

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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. © 2012 Yang et al.; licensee BioMed Central Ltd.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Yang, R Zhang, S Cotoia, A Oksala, N Zhu, S Tenhunen, J
Date:	8 May 2012
Date Type:	Publication
Journal or Publication Title:	BMC Gastroenterology
Volume:	12
DOI or Unique Handle:	10.1186/1471-230x-12-45
Schools and Programs:	School of Medicine > Critical Care Medicine
Refereed:	Yes
Date Deposited:	29 Nov 2016 21:00
Last Modified:	04 Feb 2019 22:55
URI:	http://d-scholarship.pitt.edu/id/eprint/29908

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