The roles of bilirubin and ascorbic acid as physiological antioxidant against oxidative stress.
| Project/Area Number |
07660160
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | Nagoya University |
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Principal Investigator |
HORIO Fumihiko Nagoya University, School of Agricultural Scineces, Associate Professor, 農学部, 助教授 (20165591)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Tokio Tokyo Medical and Dental University, Medical Research Institute, Associate Profe, 難治疾患研究所, 助教授 (30134745)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Bilirubin / Ascorbic acid / Oxidative stress / 抗酸化物質 / ヘムオキシゲナーゼ / インスリン依存性糖尿病 |
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| Research Abstract |
Bilirubin (BR) is synthesized from heme, and has an activity to scavenge free radicals such as reactive oxygen species (ROS). Recently, BR oxidative metabolites (BOM) were isolated from human urine, and two of them were named as biotripyrrin-a and -b. In this study, (I) we investigated the physiological role of BR as an antioxidant against oxidative stress, and (II) we examined the possibility that BOM in urine could be a metabolic marker to prodict the onset of disease that is caused by the production of ROS.
(I) The ODS rat that is a rat mutant with a hereditary defect in ascorbic acid (AsA) synthesis was intraperitoneally injected with lipopolysaccharide (LPS) whose treatment caused an oxidative stress. LPS treatment markedly increased BOM in urine, and this increase was significantly suppressed by feeding ascorbic acid. Hepatic heme oxygenase-1, which is a rate-limiting enzyme in bilirubin synthesis and is known as a protein induced by oxidative stress, was markedly induced by the LPS treatment. This induction was also suppressed by feeding ascorbic acid. These results indicated that BR acts as a physiological antioxidant synergistically with ascorbic acid against oxidative stress.
(II) Insulin-dependent diabetes (IDDM) is an autoimmune desease, and seems to be developed by the destruction of pancreatic islets caused by the production of intecellular ROS.Nonobese diabetic (NOD) mouse is an mouse model for IDDM.The increase of urinary BOM was observed in each NOD mouse between 9-week-old and 16-week-old before the development of hyperglycemia. This result suggests the possibility that the increase of BOM in urine is a metabolic marker for predicting the onset of IDDM.
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Report
(3 results)
Research Products
(12 results)
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[Publications] Yamaguchi, T., Horio, F., Hashizumi, T., Tanaka, M., Ikeda, S., Kakinuma, A.and Nakajima, H.: "Bilirubin oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid." Biochem.Biophys.Res.Commun.214. 11-19 (1995)
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[Publications] Yamaguchi, T., Terakado, M., Horio, F., Aoki, K., Tanaka, M., and Nakajima, H.: "Role of bilirubin as an antioxidant in a ischemia-reperfusion of rat liver and induction of heme oxygenase." Biochem.Biophys.Res.Commun.223. 129-135 (1996)
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[Publications] Yamaguchi, T., Hashizume, T., Tanaka, M., Nkayama, M., Sugimoto, A., Kakinuma, A., Nakajima, H.and Horio, F.: "Bilirubin oxidation evoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid." Eur.J.Biochem.(in press).
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