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.
TY - JOUR
AU - Bozic, Bojana
AU - Korać Jačić, Jelena
AU - Stanković, Dalibor M.
AU - Stanić, Marina
AU - Popovic-Bijelic, Ana
AU - Bogdanović Pristov, Jelena
AU - Spasojević, Ivan
AU - Bajčetić, Milica
PY - 2017
UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/1044
AB - 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 potentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed.
PB - Elsevier Ireland Ltd, Clare
T2 - Chemico-Biological Interactions
T1 - Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine
EP - 134
SP - 129
VL - 278
DO - 10.1016/j.cbi.2017.10.022
ER -
@article{
author = "Bozic, Bojana and Korać Jačić, Jelena and Stanković, Dalibor M. and Stanić, Marina and Popovic-Bijelic, Ana and Bogdanović Pristov, Jelena and Spasojević, Ivan and Bajčetić, Milica",
year = "2017",
abstract = "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 potentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine",
pages = "134-129",
volume = "278",
doi = "10.1016/j.cbi.2017.10.022"
}
Bozic, B., Korać Jačić, J., Stanković, D. M., Stanić, M., Popovic-Bijelic, A., Bogdanović Pristov, J., Spasojević, I.,& Bajčetić, M.. (2017). Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 278, 129-134.
https://doi.org/10.1016/j.cbi.2017.10.022
Bozic B, Korać Jačić J, Stanković DM, Stanić M, Popovic-Bijelic A, Bogdanović Pristov J, Spasojević I, Bajčetić M. Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine. in Chemico-Biological Interactions. 2017;278:129-134.
doi:10.1016/j.cbi.2017.10.022 .
Bozic, Bojana, Korać Jačić, Jelena, Stanković, Dalibor M., Stanić, Marina, Popovic-Bijelic, Ana, Bogdanović Pristov, Jelena, Spasojević, Ivan, Bajčetić, Milica, "Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine" in Chemico-Biological Interactions, 278 (2017):129-134,
https://doi.org/10.1016/j.cbi.2017.10.022 . .
