Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation
Autori
Gligorijević, NikolaVasović, Tamara
Lević, Steva M.
Miljević, Čedo
Nedić, Olgica
Nikolić, Milan
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900 mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 × 105 M−1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin ...clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced.
Ključne reči:
Binding / Coagulation / Clozapine / Fibrinogen / Hemostasis / ThrombosisIzvor:
International Journal of Biological Macromolecules, 2020, 154, 142-149Izdavač:
- Elsevier
Finansiranje / projekti:
- Strukturne karakteristike vezujućih proteina i receptora za insulinu slične faktore rasta (IGF), njihove interakcije sa drugim fiziološkim molekulima i promene kod poremećaja metabolizma (RS-MESTD-Basic Research (BR or ON)-173042)
- Racionalni dizajn i sinteza biološki aktivnih i koordinacionih jedinjenja i funkcionalnih materijala, relevantnih u (bio)nanotehnologiji (RS-MESTD-Basic Research (BR or ON)-172035)
Napomena:
- This is the peer-reviewed version of the article: Gligorijević, N.; Vasović, T.; Lević, S. M.; Miljević, Č.; Nedić, O.; Nikolić, M. Atypical Antipsychotic Clozapine Binds Fibrinogen and Affects Fibrin Formation. International Journal of Biological Macromolecules 2020, 154, 142–149. https://doi.org/10.1016/j.ijbiomac.2020.03.119
DOI: 10.1016/j.ijbiomac.2020.03.119
ISSN: 0141-8130
WoS: 000533508600016
Scopus: 2-s2.0-85081672799
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Gligorijević, Nikola AU - Vasović, Tamara AU - Lević, Steva M. AU - Miljević, Čedo AU - Nedić, Olgica AU - Nikolić, Milan PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3896 AB - Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900 mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 × 105 M−1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced. PB - Elsevier T2 - International Journal of Biological Macromolecules T1 - Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation VL - 154 SP - 142 EP - 149 DO - 10.1016/j.ijbiomac.2020.03.119 ER -
@article{ author = "Gligorijević, Nikola and Vasović, Tamara and Lević, Steva M. and Miljević, Čedo and Nedić, Olgica and Nikolić, Milan", year = "2020", abstract = "Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900 mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 × 105 M−1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced.", publisher = "Elsevier", journal = "International Journal of Biological Macromolecules", title = "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation", volume = "154", pages = "142-149", doi = "10.1016/j.ijbiomac.2020.03.119" }
Gligorijević, N., Vasović, T., Lević, S. M., Miljević, Č., Nedić, O.,& Nikolić, M.. (2020). Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in International Journal of Biological Macromolecules Elsevier., 154, 142-149. https://doi.org/10.1016/j.ijbiomac.2020.03.119
Gligorijević N, Vasović T, Lević SM, Miljević Č, Nedić O, Nikolić M. Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in International Journal of Biological Macromolecules. 2020;154:142-149. doi:10.1016/j.ijbiomac.2020.03.119 .
Gligorijević, Nikola, Vasović, Tamara, Lević, Steva M., Miljević, Čedo, Nedić, Olgica, Nikolić, Milan, "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation" in International Journal of Biological Macromolecules, 154 (2020):142-149, https://doi.org/10.1016/j.ijbiomac.2020.03.119 . .