Inhibition of histone deacetylase by butyrate protects rat liver from ischemic reperfusion injury

Int J Mol Sci. 2014 Nov 14;15(11):21069-79. doi: 10.3390/ijms151121069.


We showed previously that pretreatment of butyrate, which is an endogenous histone deacetylase (HDAC) inhibitor normally fermented from undigested fiber by intestinal microflora, seriously alleviated ischemia reperfusion (I/R)-induced liver injury by inhibiting the nuclear factor κB (NF-κB) pathway. The goal of this study was to investigate the effect of butyrate administrated at the onset of ischemia for HDAC inhibition in hepatic I/R injury. Sprague Dawley rats were subjected to warm ischemia for 60 min followed by 6 and 24 h of reperfusion. Butyrate was administrated at the onset of ischemia. Liver injury was evaluated by serum levels of aminotransferase, inflammatory factors, and histopathology. The levels of acetylated histone H3 and expression of heat shock protein (Hsp) 70 were measured by Western blot. After reperfusion, the levels of acetylated histone H3 significantly decreased. Butyrate treatment markedly prevented the reduction of acetylated histone H3 and upregulated the expression of Hsp70, thereby reducing liver injury. Our study demonstrated that I/R resulted in marked reduction of histone acetylation; butyrate exerted a great hepatoprotective effect through HDAC inhibition and Hsp70 induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects*
  • Animals
  • Butyrates / therapeutic use*
  • HSP70 Heat-Shock Proteins / metabolism
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*


  • Butyrates
  • HSP70 Heat-Shock Proteins
  • Histone Deacetylase Inhibitors
  • Histones
  • Histone Deacetylases