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<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2022-8-3-0-5</article-id><article-id pub-id-type="publisher-id">2808</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Studies to elucidate the effect and antiapoptotic mechanism of 2-ethyl-3-hydroxy-6-methylpyridine-n-acetyltaurinate in a rat model of retinal ischemia&amp;ndash;reperfusion&lt;/strong&gt;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Studies to elucidate the effect and antiapoptotic mechanism of 2-ethyl-3-hydroxy-6-methylpyridine-n-acetyltaurinate in a rat model of retinal ischemia&amp;ndash;reperfusion&lt;/strong&gt;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Efimenko</surname><given-names>Svetlana V.</given-names></name><name xml:lang="en"><surname>Efimenko</surname><given-names>Svetlana V.</given-names></name></name-alternatives><email>spotapova96@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Chernyaeva</surname><given-names>Sofia S.</given-names></name><name xml:lang="en"><surname>Chernyaeva</surname><given-names>Sofia S.</given-names></name></name-alternatives><email>sonyachernyaeva@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Peresypkina</surname><given-names>Anna A.</given-names></name><name xml:lang="en"><surname>Peresypkina</surname><given-names>Anna A.</given-names></name></name-alternatives><email>peresypkina_a@bsu.edu.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Pobeda</surname><given-names>Anna S.</given-names></name><name xml:lang="en"><surname>Pobeda</surname><given-names>Anna S.</given-names></name></name-alternatives><email>pobeda@bsu.edu.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Korokin</surname><given-names>Mikhail V.</given-names></name><name xml:lang="en"><surname>Korokin</surname><given-names>Mikhail V.</given-names></name></name-alternatives><email>mkorokin@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Beskhmelnitsyna</surname><given-names>Evgeniya A.</given-names></name><name xml:lang="en"><surname>Beskhmelnitsyna</surname><given-names>Evgeniya A.</given-names></name></name-alternatives><email>evgeny_b89@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Pokrovskii</surname><given-names>Mikhail V.</given-names></name><name xml:lang="en"><surname>Pokrovskii</surname><given-names>Mikhail V.</given-names></name></name-alternatives><email>mpokrovsky@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Ćorac</surname><given-names>Aleksandar M.</given-names></name><name xml:lang="en"><surname>Ćorac</surname><given-names>Aleksandar M.</given-names></name></name-alternatives><email>aleksandar.corac@med.pr.ac.rs</email></contrib></contrib-group><pub-date pub-type="epub"><year>2022</year></pub-date><volume>8</volume><issue>3</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2022/3/Биомедисследования_3-2022-55-64.pdf" /><abstract xml:lang="ru"><p>Background:&amp;nbsp;The study of possible ways of effective correction of retinal ischemia-reperfusion injury, which accompanies a number of eye diseases, is relevant today. The aim of the study:&amp;nbsp;To study the retinoprotective effect and antiapoptotic mechanism of 2-Ethyl-3-hydroxy-6-methyl-pyridine-N-acetyltaurinate (EHMP-NAT) in a rat model of retinal ischemia&amp;ndash;reperfusion (I/R). Materials and methods:&amp;nbsp;A pathology model with an increase in intraocular pressure (IOP) to 110 mmHg was used. The retinoprotective effect of EHMP-NAT at a dose of 4.4 mg/kg/day, in comparison with emoxipine and taurine in equimolar doses, was estimated by the changes in the retinal microcirculation, electroretinograms (the b/a coefficient), and retinal caspase-3, NF-&amp;kappa;B p65, p53 gene expressions in Wistar rats. Results:&amp;nbsp;The use of EHMP-NAT led to an increase in the retinal microcirculation level to 756.5 (median) perfusion units in comparison with emoxipine (p = 0.045) and taurine (p = 0.00029). The b/a coefficient increased in comparison with the group with emoxipine (p = 0.0099) and with the group with taurine (p = 0.015). In the group with EHMP-NAT, the caspase-3 gene expression decreased reliably in comparison with emoxipine (p = 0.0002) and with taurine (p = 0.0028); the NF-&amp;kappa;B p65 gene expression decreased in comparison with emoxipine (p = 0.0009) and with taurine (p = 0.0022); the p 53 gene expression decreased in comparison with emoxipine (p = 0.0022) and with taurine (p = 0.0009).&amp;nbsp; Conclusion:&amp;nbsp;Based on the data obtained, in correction of retinal I/R by EHMP-NAT, improvements in the retinal microcirculation, functional state, and caspase-3, NF-&amp;kappa;B p65, p53 gene expressions were more pronounced than in monotherapy with emoxipine or taurine.</p></abstract><trans-abstract xml:lang="en"><p>Background:&amp;nbsp;The study of possible ways of effective correction of retinal ischemia-reperfusion injury, which accompanies a number of eye diseases, is relevant today. The aim of the study:&amp;nbsp;To study the retinoprotective effect and antiapoptotic mechanism of 2-Ethyl-3-hydroxy-6-methyl-pyridine-N-acetyltaurinate (EHMP-NAT) in a rat model of retinal ischemia&amp;ndash;reperfusion (I/R). Materials and methods:&amp;nbsp;A pathology model with an increase in intraocular pressure (IOP) to 110 mmHg was used. The retinoprotective effect of EHMP-NAT at a dose of 4.4 mg/kg/day, in comparison with emoxipine and taurine in equimolar doses, was estimated by the changes in the retinal microcirculation, electroretinograms (the b/a coefficient), and retinal caspase-3, NF-&amp;kappa;B p65, p53 gene expressions in Wistar rats. Results:&amp;nbsp;The use of EHMP-NAT led to an increase in the retinal microcirculation level to 756.5 (median) perfusion units in comparison with emoxipine (p = 0.045) and taurine (p = 0.00029). The b/a coefficient increased in comparison with the group with emoxipine (p = 0.0099) and with the group with taurine (p = 0.015). In the group with EHMP-NAT, the caspase-3 gene expression decreased reliably in comparison with emoxipine (p = 0.0002) and with taurine (p = 0.0028); the NF-&amp;kappa;B p65 gene expression decreased in comparison with emoxipine (p = 0.0009) and with taurine (p = 0.0022); the p 53 gene expression decreased in comparison with emoxipine (p = 0.0022) and with taurine (p = 0.0009).&amp;nbsp; Conclusion:&amp;nbsp;Based on the data obtained, in correction of retinal I/R by EHMP-NAT, improvements in the retinal microcirculation, functional state, and caspase-3, NF-&amp;kappa;B p65, p53 gene expressions were more pronounced than in monotherapy with emoxipine or taurine.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>retinal ischemia–reperfusion</kwd><kwd>rats</kwd><kwd>2-ethyl-3-hydroxy-6-methyl-pyridine-n-acetyltaurinate</kwd><kwd>apoptosis</kwd></kwd-group><kwd-group xml:lang="en"><kwd>retinal ischemia–reperfusion</kwd><kwd>rats</kwd><kwd>2-ethyl-3-hydroxy-6-methyl-pyridine-n-acetyltaurinate</kwd><kwd>apoptosis</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Hardy P, Beauchamp M, Sennlaub F, et al. Inflammatory lipid mediators in ischemic retinopathy. Pharmacological Reports. 2005;57(Suppl.):169-190.</mixed-citation></ref><ref id="B2"><mixed-citation>Usui-Ouchi A, Ouchi Y, Ebihara N. The peroxisome proliferator-activated receptor pan-agonist bezafibrate suppresses microvascular inflammatory responses of retinal endothelial cells and vascular endothelial growth factor production in retinal pigmented epithelial cells. International Immunopharmacology. 2017;52:70-76. DOI: https://doi.org/10.1016/j.intimp.2017.08.027</mixed-citation></ref><ref id="B3"><mixed-citation>Xu YP, Han F, Tan J. Edaravone protects the retina against ischemia/reperfusion induced oxidative injury through the PI3K/Akt/Nrf2 pathway. Molecular Medicine Reports. 2017;16:9210-9216. DOI: https://doi.org/10.3892/mmr.2017.7739</mixed-citation></ref><ref id="B4"><mixed-citation>Nor Arfuzir NN, Agarwal R, Iezhitsa I, et al. Effect of Magnesium Acetyltaurate and Taurine on Endothelin1-Induced Retinal Nitrosative Stress in Rats. Curr Eye Res. 2018;43:1032-1040. DOI: https://doi.org/10.1080/02713683.2018.1467933.</mixed-citation></ref><ref id="B5"><mixed-citation>Peresypkina A, Pazhinsky A, Danilenko L, et al. Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate. Biology (Basel). 2020;9(3):45. DOI: https://doi.org/10.3390/biology9030045. PMID: 32121045</mixed-citation></ref><ref id="B6"><mixed-citation>Arikan S, Ersan I, Karaca T, et al. Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model. Arquivos Brasileiros de Oftalmologia. 2015;78:100-104. DOI: https://doi.org/10.5935/0004-2749.20150026</mixed-citation></ref><ref id="B7"><mixed-citation>Qin X, Li N, Zhang M, et al. Tetrahedral framework nucleic acids prevent retina ischemia-reperfusion injury from oxidative stress via activating the Akt/Nrf2 pathway. Nanoscale. 2019;11:20667-20675. DOI: https://doi.org/10.1039/c9nr07171g</mixed-citation></ref><ref id="B8"><mixed-citation>Lambuk L, Iezhitsa I, Agarwal, et al. Magnesium acetyltaurate prevents retinal damage and visual impairment in rats through suppression of NMDA-induced upregulation of NF-&amp;kappa;B, p53 and AP-1 (c-Jun/c-Fos). Neural Regeneration Research. 2021;16: 2330-2344. DOI: https://doi.org/10.4103/1673-5374.310691</mixed-citation></ref><ref id="B9"><mixed-citation>Li N, Gao S, Wang J, et al. Antiapoptotic effect of interleukin-17 in a mouse model of oxygen-induced retinopathy. Experimental Eye Research. 2019;187:107743. DOI: https://doi.org/10.1016/j.exer.2019.107743</mixed-citation></ref><ref id="B10"><mixed-citation>Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein. Current Opinion in Cell Biology. 2001;13:332-337. DOI: https://doi.org/10.1016/s0955-0674(00)00216-7</mixed-citation></ref><ref id="B11"><mixed-citation>Haupt S, Berger M, Goldberg Z, et al. Apoptosis &amp;ndash; the p53 network. Journal of Cell Science. 2003;116:4077&amp;ndash;4085. DOI: https://doi.org/10.1242/jcs.00739</mixed-citation></ref><ref id="B12"><mixed-citation>Chipuk JE, Fisher JC, Dillon CP, et al. Mechanism of apoptosis induction by inhibition of the antiapoptotic BCL-2 proteins. Proceedings of the National Academy of Sciences of the United States of America. 2008;105:20327-20332. DOI: https://doi.org/10.1073/pnas.0808036105</mixed-citation></ref><ref id="B13"><mixed-citation>Sot B, Freund SM, Fersht AR. Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the antiapoptotic BCL-xL. Journal of Biological Chemistry. 2007;282:29193-29200. DOI: https://doi.org/10.1074/jbc.M705544200</mixed-citation></ref><ref id="B14"><mixed-citation>Chen YG, Zhang C, Chiang SK, et al. Increased nuclear factor-&amp;kappa;B p65 immunoreactivity following retinal ischemia and reperfusion injury in mice. Journal of Neuroscience Research. 2003;72:125-131. DOI: https://doi.org/10.1002/jnr.10548</mixed-citation></ref><ref id="B15"><mixed-citation>Qin ZH, Chen RW, Wang Y, et al. Nuclear factor &amp;kappa;B nuclear translocation upregulates c-Myc and p53 expression during NMDA receptor-mediated apoptosis in rat striatum. Journal of Neuroscience. 1999;19:4023-4033. DOI: https://doi.org/10.1523/JNEUROSCI.19-10-04023.1999</mixed-citation></ref><ref id="B16"><mixed-citation>Voronina TA. Mexidol: The spectrum of pharmacological effects. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2012;112:86-90. Russian.</mixed-citation></ref><ref id="B17"><mixed-citation>Chesnokova NB, Beznos OV, Pavlenko TA, et al. Effects of hydroxypyridine derivatives mexidol and emoxypin on the reparative processes in rabbit eye on the models of corneal epithelial defect and conjunctival ischemia. Bulletin of Experimental Biology and Medicine. 2015;158:346-348. DOI: https://doi.org/10.1007/s10517-015-2758-3</mixed-citation></ref><ref id="B18"><mixed-citation>Manin AN, Voronin AP, Drozd KV, et al. Pharmaceutical salts of emoxypine with dicarboxylic acids. Acta crystallographica. Section C, Structural chemistry. 2018;74(7):797-806. DOI: https://doi.org/10.1107/S2053229618007386</mixed-citation></ref><ref id="B19"><mixed-citation>Keys SA, Zimmerman WF. Antioxidant activity of retinol, glutathione, and taurine in bovine photoreceptor cell membranes. Experimental Eye Research. 1999:68:693-702. DOI: https://doi.org/10.1006/exer.1999.0657</mixed-citation></ref><ref id="B20"><mixed-citation>Jafri AJA, Arfuzir NNN, Lambuk L, et al. Protective effect of magnesium acetyltaurate against NMDA-induced retinal damage involves restoration of minerals and trace elements homeostasis. Journal of Trace Elements in Medicine and Biology. 2017;39:147-154. DOI: https://doi.org/10.1016/j.jtemb.2016.09.005</mixed-citation></ref><ref id="B21"><mixed-citation>Peresypkina AA, Pokrovskii MV, Dolzhikov AA, et al. Correction of experimental ischemic neuropathy of the optic nerve by imidazoline receptor agonist type I and II. Eksperimental&amp;#39;naya i Klinicheskaya Farmakologiya. 2018;81:12-17. DOI: https://doi.org/10.30906/0869‐2092‐2018‐81‐4‐12‐17</mixed-citation></ref><ref id="B22"><mixed-citation>Chien J-Y, Lin S-F, Chou Y-Y, et al. Protective Effects of Oroxylin A on Retinal Ganglion Cells in Experimental Model of Anterior Ischemic Optic Neuropathy. Antioxidants. 2021;10:902. DOI: https://doi.org/10.3390/antiox10060902</mixed-citation></ref><ref id="B23"><mixed-citation>Peresypkina AA, Gubareva VO, Levkova EA, et al. Pharmacological correction of retinal ischemia/reperfusion by minoxidil. Srpski Arhiv Za Celokupno Lekarstvo. 2018;146:530-533. DOI: https://doi.org/10.2298/sarh170814006p</mixed-citation></ref><ref id="B24"><mixed-citation>Arfuzir NN, Lambuk L, Jafri AJ, et al. Protective effect of magnesium acetyltaurate against endothelin‐induced retinal and optic nerve injury. Neuroscience. 2016;325:153-164. DOI: https://doi.org/10.1016/j.neuroscience.2016.03.041</mixed-citation></ref><ref id="B25"><mixed-citation>McInnis J, Wang C, Anastasio N, et al. The role of superoxide and nuclear factor-kappa B signaling in N-methyl-D-aspartate-induced necrosis and apoptosis. Journal of Pharmacology and Experimental Therapeutics. 2002;301:478-487. DOI: https://doi.org/10.1124/jpet.301.2.478</mixed-citation></ref><ref id="B26"><mixed-citation>Kawamoto EM, Lima LS, Munhoz CD, et al. Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-&amp;kappa;B in the rat hippocampus. Journal of Neuroscience Research. 2012;90:213-228. DOI: https://doi.org/10.1002/jnr.22745</mixed-citation></ref><ref id="B27"><mixed-citation>Kitaoka Y, Kumai T, Kitaoka Y, et al. Nuclear factor-kappa B p65 in NMDA-induced retinal neurotoxicity. Molecular Brain Research. 2004;131:8-16. DOI: https://doi.org/10.1016/j.molbrainres.2004.07.021</mixed-citation></ref><ref id="B28"><mixed-citation>Fan W, Cooper NG. Glutamate-induced NF-&amp;kappa;B activation in the retina. Investigative Ophthalmology and Visual Science. 2009;50:917-925. DOI: https://doi.org/10.1167/iovs.08-2555</mixed-citation></ref><ref id="B29"><mixed-citation>Liebermann DA, Hoffman B, Vesely D. p53 induced growth arrest versus apoptosis and its modulation by survival cytokines. Cell Cycle. 2007;6:166-170. DOI: https://doi.org/10.4161/cc.6.2.3789</mixed-citation></ref><ref id="B30"><mixed-citation>Singh L, Pushker N, Saini N, et al. Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human retinoblastoma. Clinical and Experimental Ophthalmology. 2015;43:259-267. DOI: https://doi.org/10.1111/ceo.12397</mixed-citation></ref><ref id="B31"><mixed-citation>Lambuk L, Jafri AJ, Arfuzir NN, et al. Neuroprotective effect of magnesium acetyltaurate against NMDA-induced excitotoxicity in rat retina. Neurotoxicity Research. 2017;31:31-45. DOI: https://doi.org/10.1007/s12640-016-9658-9</mixed-citation></ref><ref id="B32"><mixed-citation>Maes ME, Schlamp CL, Nickells RW. BAX to basics: how the BCL2 gene family controls the death of retinal ganglion cells. Progress in Retinal and Eye Research. 2017;57:1-25. DOI: https://doi.org/10.1016/j.preteyeres.2017.01.002</mixed-citation></ref><ref id="B33"><mixed-citation>Riva CE, Cranstoun SD, Grunwald JE, et al. Choroidal blood flow in the foveal region of the human ocular fundus. Investigative Ophthalmology and Visual Science. 1994;35:4273-4281.</mixed-citation></ref><ref id="B34"><mixed-citation>Chamot SR, Movaffaghy AM, Petrig BL, et al. Blood flow in the human iris measured by laser Doppler flowmetry. Microvascular Research. 1999;57:153-161. DOI: https://doi.org/10.1006/mvre.1998.2136</mixed-citation></ref><ref id="B35"><mixed-citation>Riva CE, Geiser M, Petrig BL, et al. Ocular blood flow assessment using continuous laser Doppler flowmetry. Acta Ophthalmologica. 2010;88:622-629. DOI: https://doi.org/10.1111/j.1755-3768.2009.01621.x</mixed-citation></ref><ref id="B36"><mixed-citation>Schmidl D, Boltz A, Kaya S, et al. Comparison of choroidal and optic nerve head blood flow regulation during changes in ocular perfusion pressure. Investigative Ophthalmology and Visual Science. 2012;53:4337-4346. DOI: https://doi.org/10.1167/iovs.11-9055</mixed-citation></ref><ref id="B37"><mixed-citation>Mdzomba JB, Jordi N, Rodriguez L, et al. Nogo-A inactivation improves visual plasticity and recovery after retinal injury. Cell Death and Disease. 2018;9:1-14. DOI: https://doi.org/10.1038/s41419-018-0780-x</mixed-citation></ref><ref id="B38"><mixed-citation>Fischer AJ, Zelinka C, Milani‐Nejad N. Reactive retinal microglia, neuronal survival, and the formation of retinal folds and detachments. GLIA. 2015;63:313-327. DOI: https://doi.org/10.1002/glia.22752</mixed-citation></ref><ref id="B39"><mixed-citation>Novikov VE, Levchenkova OS. Promising directions of search for antihypoxants and targets of their action. Experimental and clinical pharmacology. 2013;76:37-47. Russian.</mixed-citation></ref><ref id="B40"><mixed-citation>Lambert IH, Kristensen DM, Holm JB, et al. Physiological role of taurine&amp;ndash;from organism to organelle. Acta Physiologica. 2015;213:191-212. DOI: https://doi.org/10.1111/apha.12365</mixed-citation></ref><ref id="B41"><mixed-citation>Jafri AJA, Agarwal R, Iezhitsa I, et al. Protective effect of magnesium acetyltaurate and taurine against NMDAinduced retinal damage involves reduced nitrosative stress. Molecular Vision. 2018;24:495-508.</mixed-citation></ref></ref-list></back></article>