1988 Fiscal Year Final Research Report Summary
Evaluation of antihepatotoxic drug effects using chemicals-induced cytotoxicities in primary cultured rat hepatocytes
| Project/Area Number |
61570340
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Tottori University |
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Principal Investigator |
MURA Tetuo Division of Chemistry, Institute of Steroid Research Tottori University School o, 化学部門, 講師 (80093631)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Mariko , 医学部附属ステロイド医学研究施設・化学部門, 助手 (20135883)
IKAWA Shiro , 医学部附属ステロイド医学研究施設・化学部門, 教授 (70032183)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Primary culture rat hepatocytes / Evaluation of antihepatotoxic drugs / Experimental cholestasis / Bile acid metabolism / グリチルリチンとプロトポルフィリンの薬効評価 / 加齢による核の過酸化脂質付加物 |
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| Research Abstract |
For primary screening of antihepatotoxic activity of liver-protective drugs, carbon tetrachloride- and calcium ionophore-produced cytotoxicity models utilizing primary cultured rat hepatocytes have been established. The antihepatotoxic effects of the known, such as glycyrrhizine and protoporphyrine, have been evaluated using these methods and thus devised. In the hepatocytes cultured with estradiol-17 -glucuronide (E_2-17G) induced the cholestasis-like state: The decrease of intracellular cAMP, 5'-Nase activity and taurine-conjugated bile acids and the marked increase of sulfated bile acids, especially lithocholic and chenodeoxycholic acid were obsered, while dexamethasone, phenobarbital and ursodeoxycholic acid improved these changes to the control levels.
We also observed that hepatocytes membranes affect the bile acid conjugation on enzyme induction through cell-cell contact. The induction of taurine-conjugated bile acid related to liver specific functions which are high in cells cultured at high cell density, while glycine-conjugated bile acid related to cell growth (such as glucose-6-phosphate dehydrogenase and DNA synthesis) are high at low cell density. These reciprocal regulation of bile acid conjugation may be mediated by a cell surface modulator through effects on gene expression.
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