Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine
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Stanković, Dalibor M.
Popović-Bijelić, Ana D.
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Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu2+. However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu2+ to Cu1+ in 1:1 stoichiometry. Apparently, BR undergoes degradation, i.e. BR and Cu2+ do not form stable complexes. The binding of Cu2+ to inorganic phosphates, liposomal phosphate groups, or to chelating drug penicillamine, impedes redox interactions with BR. Cu1+ undergoes spontaneous oxidation by O-2 resulting in hydrogen peroxide accumulation and hydroxyl radical production. In relation to this, copper and BR induced synergistic oxidative/damaging effects on erythrocytes membrane, which were alleviated by penicillamine. The production of reactive oxygen species by BR and copper represents a plausible cause of BR toxic effects and cell damage in hyperbilirubinemia. Further examination of therapeutic p...otentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed.
Keywords:Erythrocytes / Hydrogen peroxide / Hyperbilirubinemia / Lipid peroxidation / Superoxide
Source:Chemico-biological Interactions, 2017, 278, 129-134
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