INTERACTIONS BETWEEN BILIRUBIN AND REACTIVE OXYGEN SPECIES IN LIVER-MICROSOMES AND IN HUMAN NEUTROPHIL GRANULOCYTES

Bilirubin protects polyunsaturated fatty acids from lipid peroxidation , thus preventing damage by reactive oxygen species to cell membranes and proteins. On the other hand, such reactive oxygen species may cont ribute to the degradation and elimination of bilirubin. We therefore e xamined the interactions between bilirubin and reactive oxygen species . Bilirubin is decomposed in microsomes via a NADPH-independent proces s. this reaction appears to be mediated by H2O2 or by the hydroxyl rad ical since it is stimulated by exogenous H2O2 and by cytochrome P450 i nducers, which increase H2O2 production in microsomes, and is inhibite d by the hydroxyl radical scavenger sodium benzoate. These results sug gest that cytochrome P450 may act as a peroxidase or as a Fenton catal yst in bilirubin degradation. On the other hand, bilirubin inhibits th e NADPH consumption of microsomes as well as the NADPH oxidase activit y of human neutrophil granulocytes and the resulting superoxide format ion in these cells. This effect on superoxide concentration may be par tially due to direct interaction between superoxide and bilirubin, sin ce bilirubin reduces the superoxide concentration in a xanthine oxidas e system. Bilirubin degradation is inhibited by superoxide dismutase s uggesting that bilirubin may be oxidized in this system by the superox ide radical. The bilirubin-induced reduction in superoxide concentrati on in the supernatant of granulocytes suggests that hyperbilirubinemia may compromise immune function.