Effect of chymase inhibitor on fulminant hepatitis

• Project/Area Number: 26462050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka Medical College
• Principal Investigator: Hayashi Michihiro 大阪医科大学, 医学部, 教授 (90314179)
• Co-Investigator(Kenkyū-buntansha): 高井 真司 大阪医科大学, 医学研究科, 教授 (80288703)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 劇症肝炎 / キマーゼ / ＭＭＰ / 阻害薬 / 肥満細胞 / ハムスター / マトリックスメタロプロテアーゼ / リポポリサッカライド / D-ガラクトサミン / 酸化ストレス / 肝細胞壊死

Outline of Final Research Achievements

The effect of chymase inhibitor was investigated in fulminant hepatitis induced by lipopolysaccharide/D-galactosamine in hamsters. Hepatic chymase activity, MMP-9 activity and TNF-α concentration were extremely increased, and increases of hepatic necrosis and plasma AST and ALT were observed. Chymase inhibitor reduced not only hepatic chymase activity but also hepatic MMP-9 activity and TNF-α concentration, resulting in prevention of hepatic necrosis. Chymase inhibitor was useful to prevent the progression of fulminant hepatitis.