Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway.

• Material Type: 博士論文
• Title: Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway.
• Author/Editor: Ishida, Koji; Kaji, Kosuke; Sato, Shinya; Ogawa, Hiroyuki; Takagi, Hirotetsu; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Author Heading: Ishida, Koji; Kaji, Kosuke; Sato, Shinya; Ogawa, Hiroyuki; Takagi, Hirotetsu; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2021-03
• Publication Date (W3CDTF): 2021-03
• Alternative Title: スルフォラファンはNrf2 活性化作用を介し抗酸化ストレス作用、アセトアルデヒド代謝作用およびLPS/TLR4 シグナル経路を阻害することで四塩化炭素およびエタノール投与により誘発されるアルコール肝線維症を改善する
• Periodical title: The Journal of nutritional biochemistry
• No. or year of volume/issue: 89
• Volume: 89
• Pages: Article No.108573-
• ISSN (Periodical Title): ISSN : 0955-2863
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2022-03-15
• Dissertation Number: 甲第811号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Alcoholic liver injury; Nrf2; Sulforaphane; Mitochondrial aldehyde dehydrogenase; Lipopolysaccharide; Toll-like receptor 4
• Target Audience: 一般
• Note (General): type:Thesis; Alcoholic liver disease (ALD)-related fibrosis results from a variety of mechanisms including the accumulation of acetaldehyde, reactive oxygen species, and hepatic overload of endogenous lipopolysaccharide (LPS). Alcohol cessation is the therapeutic mainstay for patients with all stages of ALD, whereas pharmacological strategies for liver fibrosis have not been established. Sulforaphane, a phytochemical found in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts anticancer, antidiabetic, and antimicrobial effects; however, few studies investigated its efficacy in the development of ALD-related fibrosis. Herein, we investigated the effect of sulforaphane on acetaldehyde metabolism and liver fibrosis in HepaRG and LX-2 cells, human hepatoma and hepatic stellate cell lines, respectively, as well as in a mouse model of alcoholic liver fibrosis induced by ethanol plus carbon tetrachloride (EtOH/CCl₄). Sulforaphane treatment induced the activity of acetaldehyde-metabolizing mitochondrial aldehyde dehydrogenase in HepaRG cells and suppressed the acetaldehyde-induced proliferation and profibrogenic activity in LX-2 cells with upregulation of Nrf2-regulated antioxidant genes, including HMOX1, NQO1, and GSTM3. Moreover, sulforaphane attenuated the LPS/toll-like receptor 4-mediated sensitization to transforming growth factor-β with downregulation of NADPH oxidase 1 (NOX1) and NOX4. In EtOH/CCl₄-treated mice, oral sulforaphane administration augmented hepatic acetaldehyde metabolism. Additionally, sulforaphane significantly inhibited Kupffer cell infiltration and fibrosis, decreased fat accumulation and lipid peroxidation, and induced Nrf2-regulated antioxidant response genes in EtOH/CCl₄-treated mice. Furthermore, sulforaphane treatment blunted hepatic exposure of gut-derived LPS and suppressed hepatic toll-like receptor 4 signaling pathway. Taken together, these results suggest sulforaphane as a novel therapeutic strategy in ALD-related liver fibrosis.; 博士（医学）・甲第811号・令和4年3月15日; © 2020 Elsevier Inc. All rights reserved.; identifier:The Journal of nutritional biochemistry Vol.89 Article No.108573 (2021 Mar); identifier:09552863; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3994; identifier:The Journal of nutritional biochemistry, 89: Article No.108573
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.jnutbio.2020.108573
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3994/1/01%e7%94%b2811%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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