title: Protective effects of trichostatin A on liver injury in septic mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Huayu
authors.initials: H
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang