Project/Area Number |
01480228
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Gastroenterology
|
Research Institution | Nagoya City University |
Principal Investigator |
TAKEUCHI Toshihiko Nagoya City University, School of Medicine Professor, 医学部, 教授 (20079990)
|
Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Tomihiro Nagoya City University, School of Medicine Assistant, 医学部, 助手 (50172995)
KATAGIRI Kenji Nagoya City University, School of Medicine Assistant Professor, 医学部, 講師 (50094363)
|
Project Period (FY) |
1989 – 1990
|
Project Status |
Completed (Fiscal Year 1990)
|
Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥3,900,000 (Direct Cost: ¥3,900,000)
|
Keywords | Bile acid / Cholestasis / Cytoprotection / Primary cultured hepatocyte / Bile formation / Microtubule / βムリコ-ル酸 / 細胞障害 / 初代ラット培養肝細胞 / ウルソデオキシコ-ル酸 / 利胆剤 / 胆汁うっ滞 |
Research Abstract |
Cytoprotective effect of ursodeoxycholic acid (UDCA) and beta-muricholic acid (beta-MCA) were examined using isolated liver perfusion and primary cultured hepatocyte of rat. In isolated liver perfusion experiments, Taurine conjugated UDCA (TUDCA) and beta-MCA (Tbeta-MCA) can support choleresis even under condition of microtubule dysfunction, while these bile acids belong to so called micelle forming bile acid. Moreover, TUDCA and Tbeta-MCA demonstrate protective effects against taurocholate induced cholestasis of colchicine-pretreated rat liver. It was additionally found that beta-MCA stimulates bicarbonate ion excretion into bile. In the experiment using primary cultured hepatocytes, Simultaneous administration of TUDCA or Tbeta-MCA with TCA decreased LDH levels in medium and reduced TCDCA content in hepatocytes. This study revealed that TUDCA and Tbeta-MCA demonstrated its cytoprotective action through the microtubule dependent choleresis and reduction of intrahepatic content of cytotoxic bile acids.
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