Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine
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2017
Authors
Božić, BojanaKorać, Jelena
Stanković, Dalibor
Stanić, Marina
Popović-Bijelić, Ana
Pristov-Bogdanović, Jelena
Spasojević, Ivan
Bajčetić, Milica
Article (Published version)
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Show full item recordAbstract
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 / SuperoxideSource:
Chemico-biological Interactions, 2017, 278, 129-134Publisher:
- Elsevier Ireland Ltd, Clare
Funding / projects:
- Molecular mechanisms of redox signalling in homeostasis: adaptation and pathology (RS-173014)
- Study of structure-function relationships in the plant cell wall and modifications of the wall structure by enzyme engineering (RS-173017)
- Strengthening of the MagBioVin Research and Innovation Team for Development of Novel Approaches for Tumour Therapy based on Nanostructured Materials (EU-621375)
Note:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3105
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3106
DOI: 10.1016/j.cbi.2017.10.022
ISSN: 0009-2797
PubMed: 29079291
WoS: 000418302000016
Scopus: 2-s2.0-85032258652
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Institution/Community
Inovacioni centar / Innovation CentreTY - JOUR AU - Božić, Bojana AU - Korać, Jelena AU - Stanković, Dalibor AU - Stanić, Marina AU - Popović-Bijelić, Ana AU - Pristov-Bogdanović, Jelena AU - Spasojević, Ivan AU - Bajčetić, Milica PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2570 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 VL - 278 SP - 129 EP - 134 DO - 10.1016/j.cbi.2017.10.022 ER -
@article{ author = "Božić, Bojana and Korać, Jelena and Stanković, Dalibor and Stanić, Marina and Popović-Bijelić, Ana and Pristov-Bogdanović, 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", volume = "278", pages = "129-134", doi = "10.1016/j.cbi.2017.10.022" }
Božić, B., Korać, J., Stanković, D., Stanić, M., Popović-Bijelić, A., Pristov-Bogdanović, 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
Božić B, Korać J, Stanković D, Stanić M, Popović-Bijelić A, Pristov-Bogdanović 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 .
Božić, Bojana, Korać, Jelena, Stanković, Dalibor, Stanić, Marina, Popović-Bijelić, Ana, Pristov-Bogdanović, 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 . .