Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats.

Short-chain fatty acids, especially butyrate, have various biological activities including inhibition of tumor necrosis factor (TNF)-α secretion, via attenuation of nuclear factor-κB (NF-κB) activation. Here, we evaluated the protective effect of oral administration of tributyrin, a prodrug of butyrate, on lipopolysaccharide (LPS)-induced liver injury in rats. Rats were divided into four groups: normal control, tributyrin, LPS, and tributyrin/LPS (treated with tributyrin 1 h before LPS). Plasma levels of butyrate and TNF-α, expression of TNF-α, NF-κB, Toll-like receptor (TLR) 2, and TLR4 mRNA in liver, blood biochemical tests, and histopathological analysis of liver were performed. Oral tributyrin increased plasma butyrate level in the portal vein to 2.4 mM at 1 h and 0.7 mM at 2.5 h. Tributyrin attenuated NF-κB activation and liver tissue injury associated with LPS injection. The increases in TNF-α level, and hepatic TLR2 mRNA expression were lower in the tributyrin/LPS group. We believe that this study provides the first evidence that orally administered tributyrin increases butyrate level in the hepato-portal system and attenuates liver injury and subsequent inflammatory responses. Oral tributyrin increased plasma butyrate in the portal vein and attenuated liver injury in endotoxemic rats.