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

• Main Authors: Elena G. Varlamova (Author), Venera V. Khabatova (Author), Sergey V. Gudkov (Author), Egor Y. Plotnikov (Author), Egor A. Turovsky (Author)
• Format: Book
• Published: MDPI AG, 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14112477; 1999-4923
• Keywords: taxifolin; ROS; oxygen-glucose deprivation; cell death; cortex; astrocyte; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 11, p 2477 (2022)

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 H₂O₂ 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 Ca²⁺ ions in cytosol, but not OGD-induced hyperexcitation of the neuroglial network, while Se-TAX suppressed both [Ca²⁺]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 Ca²⁺ dynamics.