1998 Fiscal Year Final Research Report Summary
Clinical application of a biodefense reaction against oxidative stress using mAb.
| Project/Area Number |
09557015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo medical and dental university, Medical Research Institute |
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Principal Investigator |
YAMAGUCHI Tokio Tokyo Med.& Dent.Univ., Medical. Res.Inst., Associate Prof., 難治疾患研究所, 助教授 (30134745)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Akiko Tokyo Med.& Dent.Univ., Inst.Med.& Dent.Engineering, Res.Assistant, 医用器材研究所, 助手 (60143608)
HORIO Fumihiko Nagoya Univ., Dept.of Agriculture, Associate Prof., 農学部, 助教授 (20165591)
SUEMATSU Makoto Keio Univ.Dept.of Medicine, Associate Prof., 医学部, 助教授 (00206385)
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| Project Period (FY) |
1997 – 1998
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| Keywords | bilirubin / antioxidant / heme oxygenase / endotoxin / ascorbic acid / ELISA |
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| Research Abstract |
We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-odlod rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-odlod rats fed an ascorbicacid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection : concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5- 1O h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipo-polysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physio1ogically protective effects against oxidative stress.
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[Publications] Shinoda, Y., Suematatsu, M., Wakabayashi, Y., Goda, N., Suzuki, T., Saito, T., Yamaguchi, T., et al.: "Carbon monoxide as a regulator of bile canalicular in cultured rat hepatocytes." Hepatology. 28 (2). 286-296 (1998)
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[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)
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[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)
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