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Clinical application of a biodefense reaction against oxidative stress using mAb.

使用单克隆抗体对抗氧化应激的生物防御反应的临床应用。

基本信息

批准号：
09557015
负责人：
YAMAGUCHI Tokio
金额：
$ 0.77万
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：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557015/
关键词：
bilirubin antioxidant heme oxygenase endotoxin ascorbic acid ELISA ビリベルジン

项目摘要

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.

我们研究了胆红素氧化的可能性，在体内引起坏血病倾向的ODS odlod大鼠内毒素（脂多糖）治疗。最近，从人尿中分离出胆红素氧化代谢物，并命名为biotripyrin-a和biotripyrin-b。在ODS-odlod大鼠喂养的抗坏血酸自由饮食，尿中的胆红素代谢产物的浓度增加7.0倍，在3小时后注射脂多糖和4.4倍，在10小时相比，对照组大鼠注射生理盐水。膳食补充剂的抗坏血酸，生理抗氧化剂，抑制增加胆红素代谢产物在尿中脂多糖注射后：浓度的biotripyrin-a和biotripyrin-b在尿液中收集6.5- 10小时后，注射后低于大鼠喂食抗坏血酸补充的饮食比大鼠喂食抗坏血酸免费的饮食。此外，喂养抗坏血酸抑制肝脏血红素氧合酶-1的mRNA水平，胆红素生物合成的限速酶，在注射脂多糖的大鼠。这些结果表明，胆红素氧化显着刺激脂多糖处理的大鼠，并建议胆红素和抗坏血酸对氧化应激的生理保护作用。