High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity

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dc.contributor.author Yang, Runkuan
dc.contributor.author Zhang, Shutian
dc.contributor.author Cotoia, Antonella
dc.contributor.author Oksala, Niku
dc.contributor.author Zhu, Shengtao
dc.contributor.author Tenhunen, Jyrki
dc.date.accessioned 2012-10-09T09:38:13Z
dc.date.available 2012-10-09T09:38:13Z
dc.date.issued 2012
dc.identifier.issn 1471-230X -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66338
dc.description BioMed Central open access -
dc.description.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. -
dc.language.iso en -
dc.title High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal Article| -
dc.identifier.urn URN:NBN:fi:uta-201210091036 -
dc.identifier.doi 10.1186/1471-230X-12-45 -
dc.subject.okm fi=Kirurgia, anestesiologia, tehohoito, radiologia | en=Surgery, anesthesiology, intensive care, radiology| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title BMC Gastroenterology -
dc.journal.volume 12 -
dc.journal.number 45 -
dc.journal.volumepagerange 1-8 -
dc.journal.url http://dx.doi.org/10.1186/1471-230X-12-45 -

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