Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation
Autori
Vasović, TamaraGligorijević, Nikola
Lević, Steva M.
Miljević, Čedo
Nedić, Olgica
Nikolić, Milan
Konferencijski prilog (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Clozapine is an atypical antipsychotic used for the treatment of
schizophrenia. Prescribed daily doses of clozapine may reach
over 900 mg/day. Some studies reported a connection between
clozapine usage and the development of thrombosis. Our in vitro
study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to isolated fibrinogen, the
main protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with
affinity constant calculated to be 1.7 9 105 M1 and the number
of binding sites more than one. Direct interactions do not affect
the structure of fibrinogen, as determined by UV-VIS spectrometry and Fourier-transform infrared spectroscopy, nor fibrinogen
melting temperature, examined by fluorescence spectroscopy.
However, clozapine binding affected fibrin formation, by reducing coagulation speed and thickness of fibrin fibers. This behavior suggests that in the presence of cloza...pine, 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 individuals on clozapine treatment. By ORAC and
HORAC antioxidant assays, we found that clozapine efficiently
protects fibrinogen from free-radicals oxidation. Since the effect
of clozapine on fibrin formation is dose-dependent, it seems that
the dosage of the medication could be the main factor that determines if clozapine will have a more positive or negative effect on
fibrinogen and coagulation process in vivo.
Ključne reči:
Clozapine / FibrinogenIzvor:
FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia), 2021, 11, 181-181Izdavač:
- FEBS Open Bio © 2021 FEBS
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Vasović, Tamara AU - Gligorijević, Nikola AU - Lević, Steva M. AU - Miljević, Čedo AU - Nedić, Olgica AU - Nikolić, Milan PY - 2021 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5134 AB - Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. Prescribed daily doses of clozapine may reach over 900 mg/day. Some studies reported a connection between clozapine usage and the development of thrombosis. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to isolated fibrinogen, the main protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with affinity constant calculated to be 1.7 9 105 M1 and the number of binding sites more than one. Direct interactions do not affect the structure of fibrinogen, as determined by UV-VIS spectrometry and Fourier-transform infrared spectroscopy, nor fibrinogen melting temperature, examined by fluorescence spectroscopy. However, clozapine binding affected fibrin formation, by reducing coagulation speed and thickness of fibrin fibers. This behavior suggests 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 individuals on clozapine treatment. By ORAC and HORAC antioxidant assays, we found that clozapine efficiently protects fibrinogen from free-radicals oxidation. Since the effect of clozapine on fibrin formation is dose-dependent, it seems that the dosage of the medication could be the main factor that determines if clozapine will have a more positive or negative effect on fibrinogen and coagulation process in vivo. PB - FEBS Open Bio © 2021 FEBS C3 - FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia) T1 - Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation VL - 11 SP - 181 EP - 181 DO - doi:10.1002/2211-5463.13205 ER -
@conference{ author = "Vasović, Tamara and Gligorijević, Nikola and Lević, Steva M. and Miljević, Čedo and Nedić, Olgica and Nikolić, Milan", year = "2021", abstract = "Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. Prescribed daily doses of clozapine may reach over 900 mg/day. Some studies reported a connection between clozapine usage and the development of thrombosis. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to isolated fibrinogen, the main protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with affinity constant calculated to be 1.7 9 105 M1 and the number of binding sites more than one. Direct interactions do not affect the structure of fibrinogen, as determined by UV-VIS spectrometry and Fourier-transform infrared spectroscopy, nor fibrinogen melting temperature, examined by fluorescence spectroscopy. However, clozapine binding affected fibrin formation, by reducing coagulation speed and thickness of fibrin fibers. This behavior suggests 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 individuals on clozapine treatment. By ORAC and HORAC antioxidant assays, we found that clozapine efficiently protects fibrinogen from free-radicals oxidation. Since the effect of clozapine on fibrin formation is dose-dependent, it seems that the dosage of the medication could be the main factor that determines if clozapine will have a more positive or negative effect on fibrinogen and coagulation process in vivo.", publisher = "FEBS Open Bio © 2021 FEBS", journal = "FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia)", title = "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation", volume = "11", pages = "181-181", doi = "doi:10.1002/2211-5463.13205" }
Vasović, T., Gligorijević, N., Lević, S. M., Miljević, Č., Nedić, O.,& Nikolić, M.. (2021). Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia) FEBS Open Bio © 2021 FEBS., 11, 181-181. https://doi.org/doi:10.1002/2211-5463.13205
Vasović T, Gligorijević N, Lević SM, Miljević Č, Nedić O, Nikolić M. Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation. in FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia). 2021;11:181-181. doi:doi:10.1002/2211-5463.13205 .
Vasović, Tamara, Gligorijević, Nikola, Lević, Steva M., Miljević, Čedo, Nedić, Olgica, Nikolić, Milan, "Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation" in FEBS Open Bio, virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia), 11 (2021):181-181, https://doi.org/doi:10.1002/2211-5463.13205 . .