Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid.
We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid-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 6.5-10 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 lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.
Yamaguchi
T
T
Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Hashizume
T
T
Tanaka
M
M
Nakayama
M
M
Sugimoto
A
A
Ikeda
S
S
Nakajima
H
H
Horio
F
F
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology*; D001663:Bilirubin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001205:Ascorbic Acid; D001663:Bilirubin