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Protective effects of trichostatin A on liver injury in septic mice
Author(s) -
Zhang Li,
Wan Jingyuan,
Jiang Rong,
Wang Weiwei,
Deng Huayu,
Shen Yi,
Zheng Weiping,
Wang Yaping
Publication year - 2009
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2009.00521.x
Subject(s) - trichostatin a , sepsis , histone deacetylase , inflammation , liver injury , pharmacology , myeloperoxidase , medicine , immunology , chemistry , histone , biochemistry , gene
Aim: Acetylation is emerging as a crucial post‐translational modification in controlling the expression of eukaryotic genes. Histone deacetylase (HDAC) inhibitors, developed as antitumor reagents, have recently exhibited novel anti‐inflammatory properties. In the present study, the influence of HDAC inhibitor on hepatic injury during sepsis was investigated. Methods: Trichostatin A (TSA), a potent HDAC‐specific inhibitor, was administrated to mice with cecal ligation and puncture (CLP)‐induced sepsis. The degree of hepatic injury and inflammation was assessed subsequently. Results: The results indicated that TSA effectively protected liver from CLP‐induced injury as evidenced by decreased serum aminotransferases (alanine and aspartate) levels, reduced malondialdehyde (MDA) content in liver homogenates and improved histological damage. The dampened liver injury was accompanied by lower myeloperoxidase (MPO) activity and suppressed expression of intercellular adhesion molecule‐1 (ICAM‐1) in liver tissue. In addition, the concentrations of both interleukin (IL)‐6 and IL‐10 in serum or hepatic homogenates were also decreased in TSA‐treated septic mice. Conclusion: These data indicate that HDAC inhibitor TSA effectively attenuates liver injury during sepsis and these effects seem to rely on reduced inflammatory mediator production. These findings suggest that novel anti‐inflammatory drugs targeting HDAC might offer promising therapeutic intervention for controlling the dysregulated inflammation.