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

点击翻译按钮获取中文摘要

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.