title: Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling.
abstract: Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.
authors.affiliation: National Taiwan University College of Medicine, Taipei, Taiwan. brucelin@ntuh.gov.tw
authors.forename: Bor-Ru
authors.initials: BR
authors.lastname: Lin
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
authors.forename: Wang-Chuan
authors.initials: WC
authors.lastname: Chen
authors.forename: Hsuan-Shu
authors.initials: HS
authors.lastname: Lee
authors.forename: Huei-Min
authors.initials: HM
authors.lastname: Chang
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Lee
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Chau-Fong
authors.initials: CF
authors.lastname: Chen