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Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine. | LitMetric
Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu. However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu to Cu in 1:1 stoichiometry. Apparently, BR undergoes degradation, i.e. BR and Cu do not form stable complexes. The binding of Cu to inorganic phosphates, liposomal phosphate groups, or to chelating drug penicillamine, impedes redox interactions with BR. Cu undergoes spontaneous oxidation by O 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 potentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed.
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