Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum.

摘要: Hypochlorous acid (HOCl), an oxidant produced by myeloperoxidase (MPO), induces protein and lipid oxidation, which is implicated in the pathogenesis of atherosclerosis. Individuals with mildly elevated bilirubin concentrations (i.e., Gilbert syndrome; GS) are protected from atherosclerosis, cardiovascular disease, related mortality. We aimed to investigate whether exogenous/endogenous unconjugated (UCB), at physiological concentrations, can protect proteins/lipids oxidation induced reagent enzymatically generated HOCl. Serum/plasma samples supplemented exogenous UCB (≤250µM) were assessed for their susceptibility HOCl MPO/H2O2/Cl(-) measuring chloramine, carbonyl, malondialdehyde (MDA) formation. hyperbilirubinemic Gunn rats humans GS also exposed to: (1) validate vitro data (2) determine relevance endogenously preventing oxidation. Exogenous dose-dependently (P<0.05) inhibited MPO/H2O2/Cl(-)-induced chloramine Albumin-bound efficiently specifically (3.9-125µM; P<0.05) scavenged taurine, glycine, N-α-acetyllysine chloramines. These results translated into rat serum/plasma, showed significantly (P<0.01) reduced formation after MPO-induced Protein carbonyl MDA was MPO plasma (P<0.05; 25 50µM, respectively). Significant inhibition demonstrated within range UCB, providing a hypothetical link protection atherosclerosis individuals. demonstrate novel physiologically relevant mechanism whereby could inhibit modification quenching chloramines