Th1/Th2 balance as a determinant of drug-induced liver injury

• Project/Area Number: 20590157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: MASUBUCHI Yasuhiro Chiba Institute of Science, 薬学部, 教授 (10209455)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 副作用 / 薬剤性肝障害 / Th1 / Th2 / アセトアミノフェン / マウス / N-アセチルシステイン / インターロイキン-6 / グルタチオン / Th1/Th2 / N-フセチルシステイン / 炎症性サイトカイン / TNF-< / TNF-α

Research Abstract

Studies on susceptible and resistant mouse strains demonstrated that acetaminophen-induced liver injury was associated with Th1-dominant response in Th1/Th2 cytokine balance and increase in TNF-α/IL-6 ratio. It was confirmed by another hepatotoxicity model, which was developed by furosemide. N-Acetylcysteine and glutathione were found to exert their hepatoprotective effects via mechanisms that are independent of increasing hepatic glutathione, but probably act through improvement of Th1/Th2 balance.

Research Products

• [Journal Article] Sex difference in susceptibility to acetaminophen hepatotoxicity is reversed by buthionine sulfoximine. (2011)
  • Author(s): Masubuchi, Y., Nakayama, J., Watanabe, Y.
  • Journal Title: Toxicology in press
• [Journal Article] Protective effects of exogenous glutathione and related thiol compounds against drug-induced liver injury. (2011)
  • Author(s): Masubuchi, Y., Nakayama, J., Sadakata, Y.
  • Journal Title: Biol Pharm Bull 34 Pages: 366-370
  • NAID: 130000657814
• [Journal Article] Protective effects of exogenous glutathione and related thiol compounds against drug-induced liver injury (2011)
  • Author(s): Yasuhiro Masubuchi
  • Journal Title: Biological & pharmaceutical bulletin Volume: 34 Pages: 366-70
  • NAID: 130000657814
  • Peer Reviewed
• [Journal Article] Th1/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury. (2009)
  • Author(s): Masubuchi, Y., Sugiyama, S., Horie, T.
  • Journal Title: Chem Biol Interact 179 Pages: 273-279
• [Journal Article] Resistance to acetaminophen-induced hepatotoxicity in female CD-1 mice (2009)
  • Author(s): Yasuhiro Masubuchi
  • Journal Title: Drug Metabolism Reviews 41 Pages: 66-66
• [Journal Article] Th1/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury (2009)
  • Author(s): Yasuhiro Masubuchi
  • Journal Title: Chemico-Biological interactions 179 Pages: 273-279
  • Peer Reviewed
• [Journal Article] Th1/Th2 cytokine balance as a determinant of acetaminopher-induced liver injury. (2008)
  • Author(s): Yasuhiro Masubuchi
  • Journal Title: Chemico-biological interactions 179 Pages: 273-279
  • Peer Reviewed
• [Presentation] マウスにおける四塩化炭素誘発肝障害の性差に対するIL-6の役割 (2011)
  • Author(s): 桝渕泰宏、井原彩佳、島田薫
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] GSH合成阻害下での雌マウスのアセトアミノフェン肝障害高感受性因子の検討 (2011)
  • Author(s): 渡邉靖子、桝渕泰宏
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] Roles of glutamate-cysteine ligase and Mrp4 in gender-dependent susceptibility to acetaminophen hepatotoxicity (2010)
  • Author(s): 桝渕泰宏
  • Organizer: 日本薬物動態学会
  • Place of Presentation: さいたま
  • Year and Date: 2010-10-07
• [Presentation] アセトアミノフェン肝障害感受性の性差におけるグルタミン酸システインリガーゼとMrp4の役割 (2010)
  • Author(s): 桝渕泰宏、渡邉靖子
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: さいたま
• [Presentation] Protective effects of glutathione and the related thiols against hepatotoxicity of acetaminophen and furosemide in mice. (2010)
  • Author(s): Yasuhiro Masubuchi, Junpei Nakayama, Yuka Sadakata
  • Organizer: 16th World Congress on Basic and Clinical Pharmacology
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] アセトアミノフェン誘発肝障害に対するグルタチオンならびに関連チオール化合物の防御効果の比較 (2010)
  • Author(s): 桝渕泰宏、中山潤平、渡邉靖子
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 雌マウスにおけるアセトアミノフェン肝障害低感受性とBSO高感受性 (2010)
  • Author(s): 渡邉靖子、中山潤平、桝渕泰宏
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] Mechanisms of protection by ethynylestradiol against acetaminophen-induced hepatotoxicity in mice (2009)
  • Author(s): 桝渕泰宏
  • Organizer: 日本薬物動態学会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-28
• [Presentation] マウスにおけるエチニルエストラジオールによるアセトアミノフェン誘発肝毒性防御のメカニズム (2009)
  • Author(s): 桝渕泰宏、小林良樹、渡邉靖子
  • Organizer: 第24回日本薬物動態学会年会
  • Place of Presentation: 京都
• [Presentation] Resistance to acetaminophen-induced hepatotoxicity in female CD-1 mice. (2009)
  • Author(s): 桝渕泰宏, 中山潤平, 牧田枝里子
  • Organizer: 11th European ISSX Meeting
  • Place of Presentation: Lisbon,Portugal
• [Presentation] フロセミドによる肝障害誘発ならびにN-アセチルシステインによる防御 (2009)
  • Author(s): 桝渕泰宏、中山潤平、渡邉靖子
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] マウスにおけるアセトアミノフェン誘発肝障害の性差とその要因 (2009)
  • Author(s): 中山潤平、牧田枝里子、桝渕泰宏
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] フロセミド誘発マウス肝障害モデル : 反応性代謝物の役割ならびにアセトアミノフェンとの比較 (2008)
  • Author(s): 桝渕泰宏
  • Organizer: 第23回日本薬物動態学会
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-01
• [Presentation] フロセミド誘発マウス肝障害モデル (2008)
  • Author(s): 桝渕泰宏、浅野早紀、貞方優佳、森田雅之
  • Organizer: 第23回日本薬物動態学会年会
  • Place of Presentation: 熊本
• [Remarks] ホームページ等