Hepatoprotective effects of farnesyltransferase inhibitors and statins on liver failure

• Project/Area Number: 16K10963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kyushu University
• Principal Investigator: Shirozu Kazuhiro 九州大学, 大学病院, 講師 (30568960)
• Co-Investigator(Kenkyū-buntansha): 徳田 賢太郎 九州大学, 大学病院, 助教 (10419567)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ファルネシルトランスフェラーゼ / ファルネシル化 / スタチン / 肝不全

Outline of Final Research Achievements

Using a long-established mouse model of liver failure, we evaluated the efficacy of a farnesyltransferase inhibitor (FTI). The rapid elevation of liver deviation enzymes observed in an acute liver failure mouse model were significantly inhibited by FTI. The same inhibitory effect of FTI on liver damage was observed in actual liver sections, and in a model of liver failure, hepatocytes were impaired. The FTI significantly iInhibited expression of apoptosis and cleaved caspase 3 in liver tissue.

Academic Significance and Societal Importance of the Research Achievements

急性肝不全はある一定の確率で重症化し治療困難になりうる病態である。薬物治療では困難な場合は移植が唯一の治療手段になることもある。本研究で有効性が示されたファルネシルトランスフェラーゼ阻害薬は未だ臨床使用はされていないものの、様々な分野で有効性が示されている。今後の研究次第では臨床応用も可能だと考える。