Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine
Authors
Božić, BojanaKorać, Jelena
Stanković, Dalibor
Stanić, Marina
Popović-Bijelić, Ana
Bogdanović Pristov, Jelena
Spasojević, Ivan
Bajčetić, Milica
Article (Accepted Version)
Metadata
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-MESTD-Basic Research (BR or ON)-173014)
- Study of structure-function relationships in the plant cell wall and modifications of the wall structure by enzyme engineering (RS-MESTD-Basic Research (BR or ON)-173017)
- Strengthening of the MagBioVin Research and Innovation Team for Development of Novel Approaches for Tumour Therapy based on Nanostructured Materials (EU-FP7-621375)
Note:
- This is the peer-reviewed version of the following article: Božić, B.; Korać, J.; Stanković, D. M.; Stanić, M.; Popović-Bijelić, A.; Bogdanović Pristov, J.; Spasojević, I.; Bajčetić, M. Mechanisms of Redox Interactions of Bilirubin with Copper and the Effects of Penicillamine. Chemico-Biological Interactions 2017, 278, 129–134. https://doi.org/10.1016/j.cbi.2017.10.022
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3106
DOI: 10.1016/j.cbi.2017.10.022
ISSN: 0009-2797
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 - Bogdanović Pristov, Jelena AU - Spasojević, Ivan AU - Bajčetić, Milica PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3105 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 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", volume = "278", pages = "129-134", doi = "10.1016/j.cbi.2017.10.022" }
Božić, B., Korać, J., Stanković, D., Stanić, M., Popović-Bijelić, 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
Božić B, Korać J, Stanković D, Stanić M, Popović-Bijelić 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 .
Božić, Bojana, Korać, Jelena, Stanković, Dalibor, Stanić, Marina, Popović-Bijelić, 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 . .