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Bilirubin as a biodefense factor against oxidative stress and its clinical application

Research Project

Project/Area Number 08457045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTokyo medical and dental university, Medical Research Institute

Principal Investigator

YAMAGUCHI Tokio  Tokyo Med.& Dent.Univ., Medical.Res.Inst., Associate Prof., 難治疾患研究所・遺伝疾患(遺伝生化), 助教授 (30134745)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Akiko  Tokyo Med.& Dent.Univ., Inst.Med.& Dent.Engineerig, Res.Assistant, 医用器材研究所, 助手 (60143608)
SAITO Fumiko  Tokyo Med.& Dent.Univ., Medical.Res.Inst., Res.Assistant, 難治疾患研究所, 助手 (10158917)
HORIO Fumihiko  Nagoya Univ., Dept.of Agriculture, Associate Prof., 農学部, 助教授 (20165591)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥4,300,000 (Direct Cost: ¥4,300,000)
Keywordsoxidative stress / antioxidant / bilirubin
Research Abstract

We examined the possibility that bilirubin physiologically acts as an antioxidant by using survy-prone ODS-od/od rats treated woth endotoxin (lipopolysaccharide : LPS). Recently, billirubin oxidative metabolites were isolated from human urine, and named biotropyrrin-a and biotripyrrin-b. The LPS injection markedly increased bilirubin oxidative metabolites in urine of rats fed an ascorbic acid-free diet. This increase was suppressed by feeding an enough amount of ascorbic acid, a physiological antioxidant. The concentrations of biotripyrrin-a and -b in urine collected 6.5-10h after the LPS injection were lower in rats fed an ascorbic acid-supplemented diet than in rats fed an ascorbic acid-free diet. Moreover, feeding an ascorbic acid suppressed the elevation of hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with LPS.These findings suggest that bilirubin is oxidized in rats treated with LPS and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tokio Yamaguchi, et al.: "Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbie acid in a mutant unable to synthesize ascorbic acid." Eur.J.Biochem.245. 233-240 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuyoshi Sano, et al.: "Erdogeneous carbon monoxide suppression stimulates bile acid-deperdent biliary transport in perfused rat liver." Am.J.Physiol.272. G1268-G1275 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokio Yamaguchi, et al.: "Role of bilirubin as an antioxidant inan ischemia-reperfusion of rat liver and induction of heme oxygenase." Biochem.Biophys.Res.Commun.223. 129-135 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokio Yamaguchi, et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yuichi Shinoda.et al: "Carbon monoxide as a regulator of bilecanalicular in cultured rat hepatocytes." Hepatology. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tadashi Sakai, et al.: "Severe oxidative stress is thought to be a principal cause of jaundice of yellowtailSeriola quinqeradiata." Aquaculture. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 山口 登喜夫 他: "Free Radicals in Clinical Medicine フリーラジカルの臨床Vol.11" 日本医学館,(監修:近藤,元治), 119,79-84 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, T., Hashizume, T., Tanaka, M., Nakayama, M., Sugimoto, A., Ikeda, S., Nakajima, H., and Horio, F.: "Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid." Eur.J.Biochem. 245. 233-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sano, T., Shimomi, M., Wakabayashi, Y., Shinoda, Y., Goda, N., Yamaguchi, T., Nimura, Y., Ishimura, Y., and Suematsu, M.: "Endogeneous carbon monoxide supression stimulates bile acid-dependent biliary transport in perfused rat liver." Am.J.Physiol.G1268-G1275 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, T., M.Terakado, F.Horio, K.Aoki, M.Tanaka, and H.Nakajima: "Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase." Biochem.Biophys.Res.Commun. 223. 129-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamaguchi, T., Y.Wakabayashi, M.Tanaka, T.Sano, H.Ishikawa, H.Nakajima, M.Suematsu, et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tokio Yamaguchi, et al.: "Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbie acid in a mutant unable to synthesize ascorbic acid." Eur.J.Biochem.245. 233-240 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuyoshi Sano, et al.: "Endogeneous carbon monoxide suppression stimulates bileacid-deperdent biliary transport in perfused rat liver." Am.J.Physiol.272. G1268-G1275 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tokio Yamaguchi, et al.: "Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase." Biochem.Biophys.Res.Commun.223. 129-135 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tokio Yamaguchi.et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuichi Shinoda.et al.: "Carbon monoxide as a regulator of bile canalicular in cultured rat hepatocytes." Hepatology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tadashi Sakai.et al.: "Severe oxtdative stress is thought to be a principal cause of jaundice of yellowtail Seriola quinqeradiata." Aquaculture. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山口登喜夫 他: "Free Radicals in Clinical Medicine フリーラジカルの臨床Vol.11" 日本医学館(監修:近藤元治), 79-84 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase." Biochem.Biophys.Res.Commun.223. 129-135 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Epitope of 24G7 anti-bilirubin monoclonal antibody." Biochim.Biophys.Acta. 1289. 110-114 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Changes in the composition of bilirubin-IX isomers during human prenatal development." Eur.J.Biochem.233. 467-472 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akihiko Komuro et al.: "Cloning and characterization of the cDNA encoding human biliverdin-Xα reductase" Biochim.Biophys.Acta. 1309. 89-99 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuyoshi Sano et al.: "Carbon monoxide generated by heme oxygenase modulates biliary transport in the perfused rat liver." Am.J.Phyol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 山口登喜夫: "Free Radicals in Clinical Medicine フリーラジカルの臨床Vol.11" 日本医学館(慣習:近藤元治), 199(内)担当79-84 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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