Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/26697
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    標題: α-Lipoic acid inhibits liver fibrosis through the attenuation of ROS-triggered signaling in hepatic stellate cells activated by PDGF and TGF-β
    作者: Foo, Ning-Ping
    Lin, Shu-Huei
    Lee, Yu-Hsuan
    Wu, Ming-Jiuan
    Wang, Ying-Jan
    貢獻者: 生物科技系
    關鍵字: α-Lipoic acid
    Dihydrolipoic acid
    Liver fibrosis
    Reactive oxygen species
    Hepatic stellate cell
    日期: 2011-03
    上傳時間: 2013-06-05 16:42:53 (UTC+8)
    出版者: Elsevier
    摘要: Reactive oxygen species (ROS) have been implicated in hepatic stellate cell activation and liver fibrosis. We previously reported that α-lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) inhibited toxicant-induced inflammation and ROS generation. In the present study, we further examined the effects of LA/DHLA on thioacetamide (TAA)-induced liver fibrosis in rats and the possible underlying mechanisms in hepatic stellate cells in vitro. We found that co-administration of LA to rats chronically treated with TAA inhibited the development of liver cirrhosis, as indicated by reductions in cirrhosis incidence, hepatic fibrosis, and AST/ALT activities. We also found that DHLA inhibited TGF-β/PDGF-stimulated HSC-T6 activation and ROS generation. These effects could be mediated by the MAPK and PI3K/Akt pathways. According to our current results, LA may have a beneficial role in the treatment of chronic liver diseases caused by ongoing hepatic damage.

    Abbreviations
    HSCs, hepatic stellate cells; ROS, reactive oxygen species; α-SMA, α-smooth muscle actin; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor-β; LAα-, lipoic acid; DHLA, dihydrolipoic acid; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; JNK, c-jun N-terminal kinase; PI3K/Akt, phosphatidylinositol 3-kinase/amino kinase terminal; TAA, thioacetamide; ALT, alanine aminotransferase; AST, aspartate aminotransferase
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