| Project/Area Number |
03670632
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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 |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KUROKI Syoji KYUSHU UNIVERSITY FAC.OF MED. Assistant Professor, 医学部, 助手 (30215090)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Shuichiro KYUSHU UNIVERSITY FAC.OF MED. Assistant Professor, 医学部, 医員
ICHIMIYA Hitoshi KYUSHU UNIVERSITY FAC.OF MED. Assistant Professor, 医学部, 助手 (10183170)
CHIJIIWA Kazuo KYUSHU UNIVERSITY FAC.OF MED. Lecturer, 医学部, 講師 (90179945)
山口 幸二 九州大学, 医学部, 助手 (50191226)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Cholesterol / Carcinogenesis / 7alpha-Hydroxycholesterol / Bile acid synthesis / Oxi-cholesterolalveol / コレステロ-ル / 7αーhydroxycholesterol / 胆汁酸合成 / コレステロ-ル酸化物 |
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| Research Abstract |
In order to investigate the metabolic fate of serum esterified 7alpha -hydroxycholesterol, [4-14C]7alpha-hydroxycholesterol-3beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 hours. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 * 5.7 % (48.7 - 66.0 %) of the administered radioactivity was recovered in bile during 7 hours. The liver contained appreciable radioactivity (19.5 * 7.6 % of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 * 8.6 % (63.3 - 90.4 %). Major radioactive metabolites in the bile samples were identified to be taurine and glycine conjugated cholic acid and chenodeoxycholic acid by radio-thin layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3alpha-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha -hydroxycholesterol, and bile alcohols as well as glucuronidated or sulfated bile acids.
It is concluded that serum esterified 7alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase, and metabolized via the normal biosynthetic pathway to taurine or glycine conjugated primary bile acids to be excreted into bile.
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