Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling.
Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling.
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DOI：
10.1186/1423-0127-16-35
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发表时间：
2009-03-25
影响因子：
11
通讯作者：
Chen CF
中科院分区：
文献类型：
--
作者：
Lin BR;Yu CJ;Chen WC;Lee HS;Chang HM;Lee YC;Chien CT;Chen CF
氧化应激和炎症参与了急性肝损伤(ALI)的发生和发展。本研究旨在探讨D-氨基半乳糖(D-GalN)是否通过线粒体凋亡和促炎细胞因子信号转导途径诱导大鼠ALI，以及绿茶提取物(GT)调节细胞凋亡和促炎信号转导的可能机制(S)。D-GalN可导致肝脏缺氧/低灌流，并可从病变的肝细胞、浸润性白细胞和激活的Kupffer细胞中触发活性氧(ROS)的产生。D-半乳糖胺引起胞浆bax和线粒体细胞色素C易位，激活促炎核因子-kappaB(NF-κB)和激活蛋白-1(AP-1)易位，促进细胞间黏附分子-1表达、末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)阳性肝细胞、多种血浆细胞因子和趋化因子释放及丙氨酸氨基转移酶(ALT)活性增加。几种急性期蛋白的胆汁分泌谱的改变直接表明氧化应激影响肝细胞内的运输。GT通过增强抗细胞凋亡机制，减少ROS的产生，抑制线粒体细胞凋亡和促炎细胞因子信号通路，降低血浆ALT和细胞因子水平，减少胆汁急性期蛋白分泌，减少肝脏病理改变。综上所述，D-GalN通过缺氧/低灌流促进线粒体凋亡和促炎细胞因子信号通路诱导ALI，促进肝脏氧化应激和炎症反应。GT通过上调抗凋亡机制，抑制细胞凋亡和促炎信号转导，从而拮抗D-GalN诱导的ALI。
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-κB) 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.
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影响因子：
3.6
作者：
KEPPLER, D;LESCH, R;DECKER, K
通讯作者：
DECKER, K
DOI：
10.1073/pnas.95.25.14681
发表时间：
1998-12-08
影响因子：
11.1
作者：
Narita, M;Shimizu, S;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
影响因子：
8.8
作者：
Ritter, C;Reinke, A;Dal-Pizzol, F
通讯作者：
Dal-Pizzol, F
影响因子：
3.5
作者：
Katunuma, N;Ohashi, A;Murata, E
通讯作者：
Murata, E
影响因子：
3.4
作者：
Lin, Y;Huang, RC;Huang, RP
通讯作者：
Huang, RP