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

胆红素作为氧化应激生物防御因子及其临床应用

• 批准号: 08457045
• 负责人: YAMAGUCHI Tokio
• 金额: $ 3.52万
• 依托单位: Tokyo medical and dental university, Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457045/
• 关键词: oxidative stress; antioxidant; bilirubin

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.

我们通过使用内毒素（脂多糖：LPS）处理的易受感染的 ODS-od/od 大鼠，研究了胆红素在生理上作为抗氧化剂的可能性。最近，从人尿中分离出胆红素氧化代谢产物，并将其命名为biotropyrrin-a和biotripyrrin-b。 LPS注射显着增加了喂食无抗坏血酸饮食的大鼠尿液中的胆红素氧化代谢物。通过喂食足够量的抗坏血酸（一种生理抗氧化剂）可以抑制这种增加。注射 LPS 后 6.5-10 小时收集的尿液中生物三吡林-a 和 -b 的浓度，饲喂添加抗坏血酸饮食的大鼠低于饲喂无抗坏血酸饮食的大鼠。此外，在注射LPS的大鼠中，饲喂抗坏血酸可抑制肝血红素加氧酶-1（胆红素生物合成的限速酶）mRNA水平的升高。这些研究结果表明，在用LPS处理的大鼠中，胆红素被氧化，并在体内与抗坏血酸协同发挥生理抗氧化剂的作用。

项目成果

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Tsuyoshi Sano 等人：“抑制耳源性一氧化碳可刺激灌注大鼠肝脏中依赖于胆汁酸的胆汁运输。”

Tokio Yamaguchi, et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

Tokio Yamaguchi 等人：“牛磺胆酸盐诱导胆红素定向排泄到灌注的大鼠肝脏中的胆汁中。”

Tokio Yamaguchi et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver." Am.J.Physiol.270. G1028-G1032 (1996)

Tokio Yamaguchi 等人：“牛磺胆酸盐诱导胆红素定向排泄到灌注的大鼠肝脏中的胆汁中。”

Tokio Yamaguchi et al.: "Changes in the composition of bilirubin-IX isomers during human prenatal development." Eur.J.Biochem.233. 467-472 (1995)

Tokio Yamaguchi 等人：“人类产前发育过程中胆红素 IX 异构体的组成发生变化。”

Akihiko Komuro et al.: "Cloning and characterization of the cDNA encoding human biliverdin-Xα reductase" Biochim.Biophys.Acta. 1309. 89-99 (1996)

Akihiko Komuro 等：“编码人胆绿素-Xα 还原酶的 cDNA 的克隆和表征”Biochim.Biophys.Acta. 1309. 89-99 (1996)