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In vitro Effects of Plasma Acid on Proliferation of Rat Brain Endothelial Cells

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Abstract

The proliferative activity of brain microvascular endothelial cells is regulated by a wide range of factors: regulatory molecules, toxic compounds, cell–cell interactions. Hypervascularization and the development of oxidative and nitrosative stress are important components in the pathogenesis of chronic neurodegeneration. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), in addition to their direct damaging effect on brain cells, significantly affect the proliferative activity and angiogenic potential of brain endothelial cells. In this study, the proliferative activity of the latter was assessed in in vitro experiments performed on a primary culture of rat brain endothelial cells using the xCELLigence protocol which enables real-time monitoring of cell proliferation for 24–72 h. Aqueous ammonia and thiocyanate solutions treated with non-equilibrium (non-thermal) plasma served as sources of RNS and ROS, respectively, and were added to the culture medium at various concentrations. We found that the presence of ROS and RNS in plasma acid suppresses cell proliferation, perhaps due to the dominant effects of cytotoxic peroxynitrite and products of its interaction with cellular proteins, while the presence of ammonia in a solution stimulates cell proliferation in a dose-dependent manner. The thiocyanate anion, which is present in a freshly prepared solution, reduces the inhibitory effect of plasma acid on endothelial cell proliferation, however, prolonged exposure to plasma acid with sodium thiocyanate exhibits a considerable cytotoxic potential. Thus, plasma acid affects the proliferative activity of brain endothelial cells in vitro. This activity is modulated in the presence of ammonia and thiocyanate, suggesting the involvement of oxidative and nitrosative stress in the mechanism of plasma acid action.

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ACKNOWLEDGMENTS

The work was carried out using the resource base of the Center for Collective Use at the V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University.

Funding

This study was supported by the Ministry of Health of the Russian Federation under the state assignment to the V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University (AAAA-A19-119060690006-0).

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  1. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia

    E. D. Khilazheva, E. V. Lychkovskaya, V. A. Kutyakov, A. V. Morgun & V. V. Salmin

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  1. E. D. Khilazheva
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  2. E. V. Lychkovskaya
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  3. V. A. Kutyakov
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  4. A. V. Morgun
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Contributions

Conceptualization and experimental design (V.V.S., A.V.M., E.V.L.), data collection (E.D.Kh., A.V.M., V.A.K., V.V.S.), data processing (V.V.S., A.V.M.), writing and editing a manuscript (V.V.S.).

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Correspondence to V. V. Salmin.

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The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 7, pp. 917–930https://doi.org/10.31857/S0869813922070032.

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Khilazheva, E.D., Lychkovskaya, E.V., Kutyakov, V.A. et al. In vitro Effects of Plasma Acid on Proliferation of Rat Brain Endothelial Cells. J Evol Biochem Phys 58, 1163–1173 (2022). https://doi.org/10.1134/S0022093022040196

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