Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
[Purpose] Human serum albumin (HSA) is the most abundant protein in blood and has multi functions like maintaining plasma oncotic pressure. Previously, we demonstrated that HSA administration improves the survival rate of lethal endotoxin shock model mice. Interestingly, we has already revealed that HSA is a supersulfide in which a sulfur atom is excessively added to a thiol group and a disulfide bond. Since supersulfide possesses beneficial effects like antioxidant activity, this study was conducted to clarify the effect of supersulfide on the improvement of survival in endotoxin shock model mice by HSA.
[Methods] Lipopolysaccharide (LPS) was pretreated to RAW 264.7 cells before HSA treatment, and cystathionine β-synthase (CBS) induction and intracellular supersulfide and reactive oxygen species (ROS) levels were evaluated.
[Results and Discussion] When HSA was added to RAW264.7 cells stimulated by LPS, the expression of CBS, one of the enzymes producing supersulfide, increased. The CBS inducted by HSA increased intracellular supersulfide, and the intracellular ROS induced by hydrogen peroxide was significantly inhibited. Using endotoxin shock model mice, the effect of pretreatment with a CBS inhibitor on the HSA survival rate improvement effect was examined. As the results, the improvement effect of HSA on the survival rate almost completely cancelled by CBS inhibitor. These results suggest that HSA administration increases the intracellular supersulfide via CBS induction and improves the survival rate by reducing oxidative stress.
