%0 Journal Article
%T High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity
%A Runkuan Yang
%A Shutian Zhang
%A Antonella Cotoia
%A Niku Oksala
%A Shengtao Zhu
%A Jyrki Tenhunen
%J BMC Gastroenterology
%D 2012
%I BioMed Central
%R 10.1186/1471-230x-12-45
%X 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£¿¦Ìg per dose) or non-immune (sham) IgG every 24£¿hours for a total of 2 doses.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-¦ÊB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration.HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.
%U http://www.biomedcentral.com/1471-230X/12/45/abstract