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

Abstract

Conjugated bilirubin at low micromolar concentrations strongly inhibits the luminol-enhanced chemilu-minescence response of stimulated human polymorphonuclear leukocytes. In contrast, it does not inhibit either reduction of ferricytochrome c or lucigenin-mediated chemilum-nescence of stimulated cells. Also, conjugated bilirubin and its metabolic precursor. biliverdin, do not inhibit the enzyzme 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-CI⁻-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 α I -antiprotease against inactivation by reagent HOCl.

Key Words:

• Bilirubin
• biliverdin
• superoxide radical
• hydrogen peroxide
• hypochlorite
• αI-antipro-tease