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

BACKGROUND & AIMS: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: Oral tributyrin increased plasma butyrate in the portal vein and attenuated liver injury in endotoxemic rats.