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Article . 2019
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Chemico-Biological Interactions
Other literature type . Article . 2019 . Peer-reviewed
License: Elsevier TDM
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Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content

Authors: Uzelac, Tamara N.; Nikolić-Kokić, Aleksandra; Spasić, Snežana; Mačvanin, Mirjana T.; Nikolić, Milan; Mandić, Ljuba M.; Jovanović, Vesna B.;

Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content

Abstract

Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.

This is the peer-reviewed version of the following article: Uzelac, T. N.; Nikolić-Kokić, A. L.; Spasić, S. D.; Mačvanin, M. T.; Nikolić, M. R.; Mandić, L. M.; Jovanović, V. B. Opposite Clozapine and Ziprasidone Effects on the Reactivity of Plasma Albumin SH-Group Are the Consequence of Their Different Binding Properties Dependent on Protein Fatty Acids Content. Chemico-Biological Interactions 2019, 311. [https://doi.org/10.1016/j.cbi.2019.108787]

Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3335]

Country
Serbia
Related Organizations
Subjects by Vocabulary

Microsoft Academic Graph classification: Antioxidant medicine.medical_treatment Pharmacology chemistry.chemical_compound medicine Ziprasidone Reactivity (chemistry) Antipsychotic Clozapine Human serum albumin Binding constant chemistry Stearic acid medicine.drug

Keywords

Toxicology, Thiols, Clozapine, Albumin, General Medicine, Ziprasidone

[1] K.R. Patel, J. Cherian, K. Gohil, D. Atkinson. Schizophrenia: overview and treatment options. P. T. 39 (2014) 638-645.

[2] G. Remington. Alterations of dopamine and serotonin transmission in schizophrenia. Prog. Brain Res. 172 (2008) 117-140. https://doi.org/10.1016/S0079-6123(08)00906-0

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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download
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
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