Inhibition of Histone Deacetylase by Butyrate Protects Rat Liver from Ischemic Reperfusion Injury

Abstract

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.

Ischemia/Reperfusion

“…Based on such observations, it was hypothesized that maintaining histone acetylation would exert cardioprotective effects. Indeed, HDACs inhibition increased histone acetylation, resulting in reduced I/R injury (165, 289, 418, 654, 754, 771, 854). Similarly, treatment of cultured cardiac myocytes with siRNA targeting HDAC4 confers protection in an in vitro model of ischemic injury (288).…”

A randomized, double-blind, placebo-controlled, clinical trial on probiotic soy milk and soy milk: effects on epigenetics and oxidative stress in patients with type II diabetes

“…Dietary fiber, an effective prebiotic, can be fermented by beneficial bacteria in human's colon probiotics, and the fermentation of the fiber produces beneficial short-chain fatty acids (SCFAs) like acetate and butyrate (Cuervo et al 2013;Reimer et al 2004;Sun et al 2014). SCFAs induce chromatin remodeling by global histone acetylation and certain histones deacetylation (Worthley et al 2009;Cho et al 2014;Kuo et al 2014).…”

Molecular pathways in protecting the liver from ischaemia/reperfusion injury: a 2015 update

“…Indeed, warm hepatic I/R injury is accompanied by a significant reduction in histone acetylation in the liver, suggesting that histone acetylation may play an important role in I/R injury representing a new therapeutic strategy to ameliorate this pathology [28]. Protein acetylation by histone acetyltransferases enhances gene expression via relaxation of chromatin and transcription activation.…”