| Project/Area Number |
63571080
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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 |
医学一般
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| Research Institution | Tokyo Metropolitan Geriatric Institute |
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Principal Investigator |
TSURU Masanobu Tokyo Metropolitan Geriatric Institute, 臨床生理2, 研究員 (30145362)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Haruhiko The 2nd Department of Internal Medicine, University of Tokyo, 医学部・第二内科, 医師
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Bilirubin / Free radical / Xanthine oxidase / SOD / Catalase / Ascorbic acid / Isolated hepatocytes / 四塩化炭素 / 肝障害 / 過酸化脂質 / スーパーオキサイドディスミュテース |
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| Research Abstract |
Various stimuli to the body including oxidative stress cause organ damage. Halogenated hydrocarbons,carbon tetrachloride being the most well-known, are good models for studying free-radical mediated liver injury.
Bilirubin, the end product of heme catabolism in mammals, is generally regarded as a potentially cytotoxic compound which is only to be excreted. However, it has also been suggested that the bile pigments bilirubin and biliverdin may protect vitamin A and linoleic acid from oxidative destruction in the intertinal tract. Because bilirubin contains an extended system of conjugated double bonds and a reactive hydrogen atom which may possess an antioxidant properties.
We examined the antioxidative properties of bilirubin using hypoxanthine/xanthine oxidase system and isolated hepatocites.
(METHODS) lOmM hypoxanthine and 50 mM xanthine oxidase were mixed and 10 ILM bilirubin was added. Absorbance at 444 and 656 nm was monitored for 10min. Decrease of absorbance at 444 nm was regarded as destruction of bilirubin by free radicals. Effects superoxide dismutase, catalase, dimethylsulfoxide and ascorbin acid on the decrease of absorbance at 444 nm was studied. Isolated hepatocytes were prepared by using coliagenase and were labeled with Cr. Hypoxanthine/xanthine oxidase system was added to the isolated hepatocytes and effects of bilirubin on the release of Cr was studied. (RESULTS and DISCUSSIONS) Hypoxanthine/xanthine systems caused the decrease of bilirubin observed at 444 nm. Decrease of bilirubin was inhibited by superoxide dismutase and ascorbin acid. Release of Cr was enhanced by hypoxanthine/xanthine oxidase. Blirubin inhibited the release of Cr from the isolated hepatocyts. These data suggest that bilirubin possesses an antioxidant propertied and protect hepatocytes from oxidative stress.
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