Taurine protects transplanted liver against ischemia-reperfusion injury

ABSTRACT

Although liver transplantation as a treatment of end-stage liver disease has developed rapidly, the problem of ischemia-reperfusion injury [I/RI] to the liver graft remains an obstacle. After I/R, Kupffer cells were activated and generate reactive oxygen species [ROS] which play a central role in the pathogenesis of rejection. Taurine is a cysteine derivative known as being a conjugate to primary bile acids; besides oxidative regulation functions, it is supposed to have protective efficacy on ischemia reperfusion liver damage and its anti-hepatic injury may be mainly related to inhibiting lipid peroxides formation, regulating cellular calcium homeostasis and stabilizing biological membrane. To evaluate the effect of taurine injection before liver transplantation on the oxidant [MDA] /antioxidant [reduced glutathione and glutathione peroxidase] status, activation of Kupffer cell [tumor necrosis factor-alpha] and cell apoptosis [expression of hypoxia inducible factor-1 alpha [HIF-1 alpha] and caspase-3]. Forty patients undergoing liver transplantation were divided into two groups Group I Taurine group [n=20] were given [1 gm taurine intravenous bolus to the donor 30 min before hepatectomy and another 1 gm to recipient 15 min before graft reperfusion] .Group II saline control group [n= 20] were given physiological saline of the same volume as taurine group. Liver biopsy was taken before the end of operation for the mRNA expression of HIF-1 alpha and caspase-3. Blood samples were taken from each participant at the beginning of the operation [T[0]], clamping of portal vein [T[1]], 1 h and 3 h after portal vein reperfusion [T[2] and T[3], respectively]. Serum levels of aspartate aminotransferase [AST], alanine aminotransferase [ALT], tumor necrosis factor-alpha [TNF- alpha], malondialdehyde [MDA], reduced glutathione [GSH] and whole blood glutathione peroxidase activity [GPx] were analyzed. TNF-alpha and MDA levels were significantly increased at T[1], significantly peaked at 1 h after reperfusion [T[2]] and significantly decline after 3h [T[3]]. However, this elevation of TNF-alpha and MDA levels were significantly higher in saline group compared to taurine group. On the other hand, the level of GSH and the activity of GPx were significantly higher in the taurine group than in the control group. HIF-1 alpha and caspase-3 mRNA were highly expressed in control group more than taurine group. Taurine can protect the liver against ischemia-reperfusion injury by downregulation of HIF-1alpha, caspase-3, decreasing the production of TNF-alpha and improvement of hepatic antioxidant capacity