Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling

Acute liver injury (ALI) may cause dismal clinical outcome [1,2], but the detailed pathophysiologic mechanisms and the preventive and therapeutic medications have not been fully elucidated. In all types of liver damage there is consistent evidence of enhanced oxidative stress and/or significant decrease of antioxidant defense [2]. Oxidative stress and inflammation have been reported to contribute to the pathogenesis of alcohol-, CCl4-, thioacetamide- and endotoxin-induced ALI [2-6]. D-galactosamine (D-GalN) treated livers have metabolic and morphological aberrations similar to those observed in human viral hepatitis that always caused peri-portal necro-inflammation [7,8] and hepatocyte apoptosis [9]. Although D-GalN was well-known to induce toxicity by blocking RNA and protein synthesis [7,8], its ability to induce oxidative injury in the liver was still poorly delineated.Reactive oxygen species (ROS) play a crucial role in the induction and in the progression of liver disease. In response to hypoxia/hypoperfusion or toxic injury, a massive ROS production can cause lipid peroxidation of cellular membranes, and protein and DNA oxidation, which results in cellular injury [2,10-14]. The main sources of ROS may derive from the mitochondria of hepatocytes, the activated macrophages (Kupffer cells), and the infiltrating neutrophils [2,11-14]. These ROS can trigger the translocation of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) to nucleus [12] and activation of inflammatory cytokines, chemokines, and adhesion molecules that, in turn, can contribute to further production of ROS [2,6,14] and consecutively activate the cascade of Bax and cytochrome c translocation and caspases (apoptosis) [15]. Various kinds of antioxidants capable of decreasing NF-κB activity, ameliorating mitochondrial dysfunction, cytochrome c release and caspase-3-mediated apoptosis, and decreasing inflammatory cell infiltration [2-5,15-17] have been shown to reduce tissue injury. Recen