Butyrate Protects Rat Liver against Total Hepatic Ischemia Reperfusion Injury with Bowel Congestion

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.

Protective Effects of Butyrate on Renal Ischemia-Reperfusion Injury in Rats

“…Since butyrate suppresses histone deacetylase, it was widely used as a therapeutic agent in patients with cancer [8][9][10][11]. A series of studies have reported that in addition to its anticancer activity, butyrate possesses potent anti-inflammatory and antiapoptotic effects, as well as markedly attenuates free radical formation [9,[12][13][14]. More recently, reports have demonstrated that butyrate may protect diverse organs against IRI [13][14][15][16].…”

“…A series of studies have reported that in addition to its anticancer activity, butyrate possesses potent anti-inflammatory and antiapoptotic effects, as well as markedly attenuates free radical formation [9,[12][13][14]. More recently, reports have demonstrated that butyrate may protect diverse organs against IRI [13][14][15][16]. For example, Sun et al [14] reported the neuroprotective effects of butyrate against cerebral IRI in an in vivo murine model.…”

“…Rats were injected intravenously with 300 mg/kg of sodium butyrate (SigmaAldrich, St. Louis, MO, USA) in the butyrate group or a saline solution in the sham and IRI groups 30 min before renal ischemia. The dose and route of butyrate in this study were chosen based on previous reports, and a preliminary study was conducted [13,15].…”

“…Previous studies have reported the anticancer effects of butyrate [8,11]. More recently, butyrate has been investigated as a potential therapeutic agent for diseases associated with IRI because of its anti-Urol Int 2019;102:348-355 DOI: 10.1159/000497476 oxidant, anti-inflammatory, and antiapoptotic effects in vivo and in vitro [12][13][14]. Liu et al [15] reported that butyrate reduced hepatic IRI in rats by attenuating oxidative stress and apoptosis.…”

“…More recently, butyrate has been investigated as a potential therapeutic agent for diseases associated with IRI because of its anti-Urol Int 2019;102:348-355 DOI: 10.1159/000497476 oxidant, anti-inflammatory, and antiapoptotic effects in vivo and in vitro [12][13][14]. Liu et al [15] reported that butyrate reduced hepatic IRI in rats by attenuating oxidative stress and apoptosis. In an in vivo murine model, Qiao et al [16] reported the protective effects of butyrate on intestinal IRI because of the inhibition of inflammation.…”