Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.
We examined the possibility that bilirubin physiologically acts as an antioxidant by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-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 supressed by feeding an adequate amount of ascorbic acid, a physiological antioxidant. the concentrations of biotripyrrin-a and -b in urine collected 6.5-10 h 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 with 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.
Yamaguchi
T
T
Department of Biochemical Genetics, Tokyo Medical and Dental University, Japan.
Horio
F
F
Hashizume
T
T
Tanaka
M
M
Ikeda
S
S
Kakinuma
A
A
Nakajima
H
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000097:blood / Q000502:physiology*; D001483:Base Sequence; D001663:Bilirubin / Q000378:metabolism* / Q000502:physiology / Q000652:urine; D016166:Free Radical Scavengers; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012614:Scurvy / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D001205:Ascorbic Acid; D001663:Bilirubin