2 PATHWAYS OF IRON-CATALYZED OXIDATION OF BILIRUBIN - EFFECT OF DESFERRIOXAMINE AND TROLOX, AND COMPARISON WITH MICROSOMAL OXIDATION

The bilirubin-degrading activity of liver microsomes from rats induced with 3-methylcholanthrene has been shown to be markedly stimulated by addition of 3,3',4,4',5,5'-hexabromobiphenyl, a polyhalogenated chemical which resembles in size and shape the most effective inducers of cytochrome P450IA1, but lacks the structural features necessary for it to be metabolised. The degradation of bilirubin by this microsomal system has been compared to oxidation by a chemical model system involving H2O2 and Fe-EDTA (ethylenediaminetetraacetic acid). In both systems bilirubin disappearance was accompanied by bleaching. However, when either desferrioxamine or Trolox were present in the chemical model system, the rate of bilirubin oxidation was greatly enhanced and, at the same time, bilirubin was largely or entirely converted to biliverdin, a pathway of oxidation which proceeds by dehydrogenation. In the presence of desferrioxamine, biliverdin was also further oxidised to an unidentified red pigment.