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.