Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase.
The anti-oxidative effect of bilirubin was investigated in an ischemia-reperfusion model of rat liver. The rat portal vessel and liver artery were ligated with a vascular clip, and after reperfusion the urine was collected at intervals. The amount of biopyrrins, the oxidative metabolites of bilirubin, in rat urine reached a maximum 4 hours after reperfusion. Biotripyrrin-a and -b which are biopyrrins isolated from human urine were included in urinary bilirubin oxidative metabolites of rats after reperfusion. The hepatic mRNA level of heme oxygenase-1 (HO-1), the rate limiting enzyme of bilirubin biosynthesis, reached a maximum after 4 hours. Furthermore, the hepatic activity of HO began to rise 4 hours after treatment and remained high until 24 hours posttreatment. These findings suggest that bilirubin acts as a physiological antioxidant in vivo in ischemia-reperfusion and that bilirubin biosynthesis is evoked by oxidative stress.
Yamaguchi
T
T
Department of Biochemical Genetics, Tokyo Medical and Dental University, Japan.
Terakado
M
M
Horio
F
F
Aoki
K
K
Tanaka
M
M
Nakajima
H
H
D000818:Animals; D000975:Antioxidants; D001663:Bilirubin / Q000502:physiology* / Q000652:urine; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000503:physiopathology*; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress; D011758:Pyrroles / Q000652:urine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015424:Reperfusion; D013997:Time Factors; D014158:Transcription, Genetic
D000975:Antioxidants; D011758:Pyrroles; D012333:RNA, Messenger; C099842:biotripyrrin a; C099843:biotripyrrin b; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione; D001663:Bilirubin