Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion

PLoS One. 2014 Aug 29;9(8):e106184. doi: 10.1371/journal.pone.0106184. eCollection 2014.

Abstract

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Butyrates / therapeutic use*
  • Constipation / complications*
  • Constipation / immunology
  • Constipation / pathology
  • Constipation / prevention & control
  • Cytokines / immunology
  • Endotoxins / immunology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Liver / drug effects
  • Liver / immunology
  • Liver / pathology
  • Liver Diseases / complications*
  • Liver Diseases / immunology
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Male
  • Neutrophil Infiltration / drug effects
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • Anti-Inflammatory Agents
  • Butyrates
  • Cytokines
  • Endotoxins
  • Protective Agents

Grant support

This study was supported by the National Natural Science Foundation of China (NO81270530) and Specialized Research Fund for the Health Care (NO201002004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.