Antioxidant Properties of Conjugated Bilirubin and Biliverdin: Biologically Relevant Scavenging of Hypochlorous Acid

Conjugated bilirubin at low micromolar concentrations strongly inhibits the luminol-enhanced chemiluminescence response of stimulated human polymorphonuclear leukocytes. In contrast, it does not inhibit either reduction of ferricytochrome c or lucigenin-mediated chemiluminescence of stimulated cells. Also, conjugated bilirubin and its metabolic precursor, biliverdin, do not inhibit the enzyme myeloperoxidase (MPO) since (i) the MPO-dependent oxidation of guaiacol is not affected by biliverdin and (ii) the spectral changes observed when conjugated bilirubin is oxidized by a MPO-H2O2-Cl(-)-system are very similar to those obtained with reagent HOCl. As judged from these spectroscopic studies, each molecule of conjugated bilirubin can scavenge one molecule of HOCl giving rise to an oxidation product that itself is capable of scavenging further molecules of HOCl. Importantly, at physiological pH, both bile pigments can efficiently protect the elastase-inhibitory capacity of alpha 1-antiprotease against inactivation by reagent HOCl.