Objective: We determined whether there is a protective effect of branched-chain amino acid (BCAA) on hepatic ischemia/reperfusion (IR)-induced acute liver injury. Methods: Wister rats were divided into four groups: simple laparotomy with vehicle; simple laparotomy with BCAA (1 g/kg of body weight orally); IR (30 min clamp) with vehicle; and IR with BCAA. Serum liver function tests and the gene expression of adhesion molecules (ICAM and VCAM) and vasoconstrictor-related genes (endothelin-1) in the liver were examined. In the in vivo study, portal venous pressure, leukocyte adhesion, and hepatic microcirculation were evaluated. Furthermore, Kupffer cells were isolated and cultured with various concentrations of BCAA in the presence or absence of lipopolysaccharide (LPS). Results: Increased levels of liver function tests following IR were significantly attenuated by BCAA treatment. The increased expression of adhesion molecules and endothelin-1 were also significantly attenuated by BCAA treatment. Moreover, increased portal venous pressure, enhanced leukocyte adhesion, and deteriorated hepatic microcirculation following IR were all improved by BCAA treatment. In the experiment using isolated Kupffer cells, the expression of interleukin-6, interleukin-1β, and endothelin-1 in response to LPS stimulation was attenuated by BCAA in a dose-dependent fashion. Conclusions: These results indicate that perioperative oral administration of BCAA has excellent therapeutic potential to reduce IR-induced liver injury. These beneficial effects may result from the direct attenuation of Kupffer cell activation under stressful conditions.
- inflammatory responses
- microcirculatory failure
- Copyright © 2012, American Journal of Physiology- Gastrointestinal and Liver Physiology