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Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation

The neuroprotective effect of the natural antioxidant taxifolin (TAX) is well known for ischemic pathologies. However, the limitations of taxifolin application are described—poor solubility, low ability to penetrate the blood–brain barrier, and side effects from high doses for stroke therapy. We pro...

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Autores principales: Varlamova, Elena G., Khabatova, Venera V., Gudkov, Sergey V., Plotnikov, Egor Y., Turovsky, Egor A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697510/
https://www.ncbi.nlm.nih.gov/pubmed/36432668
http://dx.doi.org/10.3390/pharmaceutics14112477
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author Varlamova, Elena G.
Khabatova, Venera V.
Gudkov, Sergey V.
Plotnikov, Egor Y.
Turovsky, Egor A.
author_facet Varlamova, Elena G.
Khabatova, Venera V.
Gudkov, Sergey V.
Plotnikov, Egor Y.
Turovsky, Egor A.
author_sort Varlamova, Elena G.
collection PubMed
description The neuroprotective effect of the natural antioxidant taxifolin (TAX) is well known for ischemic pathologies. However, the limitations of taxifolin application are described—poor solubility, low ability to penetrate the blood–brain barrier, and side effects from high doses for stroke therapy. We proposed the problem of targeted delivery of taxifolin and achievement effective concentrations could be solved by developing a nanocomplex of selenium nanoparticles (SeNPs) with taxifolin (Se–TAX). In this study, we developed a selenium–taxifolin nanocomplex based on selenium nanoparticles with a 100 nm size. It was shown that TAX, SeNPs, and Se–TAX were all able to suppress the production of ROS in neurons and astrocytes under exposure to exogenous H(2)O(2) and ischemia-like conditions. However, the Se–TAX nanocomplex appeared to be the most effective, displaying a lower working concentration range and negligible pro-oxidant effect compared with pure SeNPs. The mechanism of Se–TAX beneficial effects involved the activation of some antioxidant enzymes and the suppression of ROS-generating systems during OGD/reoxygenation, while TAX and “naked” SeNPs were less effective in regulating the cellular redox status. Naked SeNPs inhibited a global increase in Ca(2+) ions in cytosol, but not OGD-induced hyperexcitation of the neuroglial network, while Se–TAX suppressed both [Ca(2+)]i rise and hyperexcitation. The effect of TAX at similar doses appeared exclusively in inhibiting OGD-induced hyperexcitation. Analysis of necrosis and apoptosis after OGD/reoxygenation revealed the highest efficiency of the Se–TAX nanocomplex as well. Se–TAX suppressed the expression of proinflammatory and proapoptotic proteins with simultaneous activation of protective genes. We conclude that the Se–TAX nanocomplex combines the antioxidative features taxifolin and the antiapoptotic effect of nanoselenium, involving the regulation of Ca(2+) dynamics.
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spelling pubmed-96975102022-11-26 Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation Varlamova, Elena G. Khabatova, Venera V. Gudkov, Sergey V. Plotnikov, Egor Y. Turovsky, Egor A. Pharmaceutics Article The neuroprotective effect of the natural antioxidant taxifolin (TAX) is well known for ischemic pathologies. However, the limitations of taxifolin application are described—poor solubility, low ability to penetrate the blood–brain barrier, and side effects from high doses for stroke therapy. We proposed the problem of targeted delivery of taxifolin and achievement effective concentrations could be solved by developing a nanocomplex of selenium nanoparticles (SeNPs) with taxifolin (Se–TAX). In this study, we developed a selenium–taxifolin nanocomplex based on selenium nanoparticles with a 100 nm size. It was shown that TAX, SeNPs, and Se–TAX were all able to suppress the production of ROS in neurons and astrocytes under exposure to exogenous H(2)O(2) and ischemia-like conditions. However, the Se–TAX nanocomplex appeared to be the most effective, displaying a lower working concentration range and negligible pro-oxidant effect compared with pure SeNPs. The mechanism of Se–TAX beneficial effects involved the activation of some antioxidant enzymes and the suppression of ROS-generating systems during OGD/reoxygenation, while TAX and “naked” SeNPs were less effective in regulating the cellular redox status. Naked SeNPs inhibited a global increase in Ca(2+) ions in cytosol, but not OGD-induced hyperexcitation of the neuroglial network, while Se–TAX suppressed both [Ca(2+)]i rise and hyperexcitation. The effect of TAX at similar doses appeared exclusively in inhibiting OGD-induced hyperexcitation. Analysis of necrosis and apoptosis after OGD/reoxygenation revealed the highest efficiency of the Se–TAX nanocomplex as well. Se–TAX suppressed the expression of proinflammatory and proapoptotic proteins with simultaneous activation of protective genes. We conclude that the Se–TAX nanocomplex combines the antioxidative features taxifolin and the antiapoptotic effect of nanoselenium, involving the regulation of Ca(2+) dynamics. MDPI 2022-11-16 /pmc/articles/PMC9697510/ /pubmed/36432668 http://dx.doi.org/10.3390/pharmaceutics14112477 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Varlamova, Elena G.
Khabatova, Venera V.
Gudkov, Sergey V.
Plotnikov, Egor Y.
Turovsky, Egor A.
Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title_full Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title_fullStr Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title_full_unstemmed Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title_short Cytoprotective Properties of a New Nanocomplex of Selenium with Taxifolin in the Cells of the Cerebral Cortex Exposed to Ischemia/Reoxygenation
title_sort cytoprotective properties of a new nanocomplex of selenium with taxifolin in the cells of the cerebral cortex exposed to ischemia/reoxygenation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697510/
https://www.ncbi.nlm.nih.gov/pubmed/36432668
http://dx.doi.org/10.3390/pharmaceutics14112477
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