AbstractsBiology & Animal Science

Branched chain amino acid supplementation modulates the effect of inflammatory mediators on the function of a hepatoma cell line

by Sharareh Hashemi

Institution: Rutgers University
Department: Biomedical Engineering
Degree: MS
Year: 2013
Keywords: Branched chain amino acids; Wounds and injuries – Complications; Inflammation – Mediators
Record ID: 1995055
Full text PDF: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000068877


Severe trauma injuries often lead to a prolonged inflammatory response associated with metabolic abnormalities. These abnormalities lead to persistent skeletal muscle proteolysis and rapid loss of lean body mass, which may lead to multiple organ dysfunction and death. The liver plays an important role in this systemic response to injury by modulating the inflammatory processes, immune functions, and metabolic pathways. The acute phase of the response is characterized by the release of inflammatory mediators, including proinflammatory cytokines and reactive oxygen species (ROS), as well as a change in the protein secretion pattern and increased amino acid utilization by the liver. When these changes persist for long periods of time, they likely contribute to the body’s negative nitrogen balance as well as loss of lean body mass (LBM). Among all proteins secreted by the liver, albumin is the most abundant one and its secretion rate significantly decreases in inflammatory states, and results in a lower circulating concentration in patients. Albumin provides the critical colloid osmotic pressure to regulate the passage of water and diffusible solutes through the capillaries. Increased utilization of amino acids in trauma is thought to be important for defense against diseases; however, it reduces body stores of proteins and free amino acids to supply amino acid needs for tissue repair, acute phase protein production, and gluconeogenesis. Nutritional supplementation is currently being used to alleviate endogenous nitrogen depletion and to maximize protein synthesis for optimal wound healing and immune function. Among nutritional supplements, there has been increased interest in using branched chain amino acids (BCAAs), and clinical studies suggest that BCAAs can enhance liver function in inflammatory states. The mechanism whereby BCAAs impact the liver function during inflammation is unclear. The purpose of this research is to investigate the effect of proinflammatory mediators (more specifically the cytokines interleukin-1ß & interleukin-6) and reactive oxygen species H₂O₂, and BCAAs on a cell culture model of liver consisting of HepG2/C3A hepatoma cells. It was found that these mediators reversibly suppressed albumin and urea production in a dose-dependent manner, and also decreased the amount of the intracellular antioxidant reduced glutathione. BCAA supplementation mitigated the effect of these inflammatory mediators; however, this effect was maximized at a relatively low concentration of BCAAs, above which no further benefit was observed. Therefore, BCAAs are potentially beneficial to support liver function during inflammation.