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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Science and Innovations in Medicine</journal-id><journal-title-group><journal-title xml:lang="en">Science and Innovations in Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Наука и инновации в медицине</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2500-1388</issn><issn publication-format="electronic">2618-754X</issn><publisher><publisher-name xml:lang="en">FSBEI of Higher Education SamSMU of Ministry of Health of the Russian Federation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">110765</article-id><article-id pub-id-type="doi">10.35693/2500-1388-2022-7-3-206-211</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Pharmacology</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Фармакология, клиническая фармакология</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Metabolic effects of 3-substituted chromone derivatives in experimental chronic traumatic encephalopathy</article-title><trans-title-group xml:lang="ru"><trans-title>Метаболические эффекты 3-замещенных производных хромона в условиях экспериментальной хронической травматической энцефалопатии</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5595-8182</contrib-id><name-alternatives><name xml:lang="en"><surname>Pozdnyakov</surname><given-names>Dmitrii I.</given-names></name><name xml:lang="ru"><surname>Поздняков</surname><given-names>Дмитрий Игоревич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, Associate professor, Department of Pharmacology with a course of clinical pharmacology</p></bio><bio xml:lang="ru"><p>канд. фарм. наук, доцент кафедры фармакологии с курсом клинической фармакологии</p></bio><email>pozdniackow.dmitry@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Pyatigorsk Medical-Pharmaceutical Institute – branch of Volgograd State Medical University</institution></aff><aff><institution xml:lang="ru">Пятигорский медико-фармацевтический институт – филиал ФГБОУ ВО «Волгоградский государственный медицинский университет» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-09-04" publication-format="electronic"><day>04</day><month>09</month><year>2022</year></pub-date><volume>7</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>206</fpage><lpage>211</lpage><history><date date-type="received" iso-8601-date="2022-09-04"><day>04</day><month>09</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2022-09-04"><day>04</day><month>09</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Pozdnyakov D.I.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Поздняков Д.И.</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Pozdnyakov D.I.</copyright-holder><copyright-holder xml:lang="ru">Поздняков Д.И.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://innoscience.ru/2500-1388/article/view/110765">https://innoscience.ru/2500-1388/article/view/110765</self-uri><abstract xml:lang="en"><p><bold>Aim</bold> – to evaluate the effect of five new 3-substituted chromone derivatives on changes in mitochondrial function and the development of tau pathology in animals under experimental chronic traumatic encephalopathy.</p> <p><bold>Material and methods. </bold>Chronic traumatic encephalopathy was modeled in Wistar rats by repeated exposure to a shock wave (2 atm.) on the animal's head for seven days. The studied compounds (X3A1 – X3A5) and the reference citicoline were administered 60 minutes after injury at doses of 40 mg/kg and 150 mg/kg orally. On the eighth day of the experiment, changes in the mass coefficient of the brain, the concentration of phosphorylated tau protein in brain tissue and changes in the activity of cytochrome-c-oxidase and succinate dehyrogenase were evaluated in animals.</p> <p><bold>Results.</bold> The use of compounds X3A4 and X3A5 equally to citicoline reduced the development of tau pathology, increased the activity of mitochondrial enzymes: cytochrome-c-oxidase – by 14.5% (p&lt;0.05), 41.9% (p&lt;0.05) and 22.6% (p&lt;0.05), respectively; succinate dehydrogenase – by 28.6% (p&lt;0.05); 33.2% (p&lt;0.05) and 22.8% (p&lt;0.05), respectively. As a result, against the background of the administration of these compounds, an increase in brain mass coefficient was noted in relation to the animals that did not receive a pharmacological support.</p> <p><bold>Conclusion.</bold> Administration of chromone derivatives X3A4 and X3A5 to animals with experimental chronic traumatic encephalopathy prevents the development of tau pathology and atrophy of brain tissue, probably due to metabolic action, expressed in the restoration of mitochondrial function.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Цель</bold> – оценить влияние пяти новых 3-замещенных производных хромона на изменение митохондриальной функции и развитие тау-патологии у животных в условиях хронической травматической энцефалопатии.</p> <p><bold>Материал и методы. </bold>Хроническую травматическую энцефалопатию моделировали у крыс линии Wistar путем повторяющегося воздействия ударной волны сжатого воздуха (2 атм.) на голову животного на протяжение семи дней. Изучаемые соединения (Х3А1 – Х3А5) и препарат сравнения цитиколин вводили через 60 минут после нанесения травмы в дозах 40 мг/кг и 150 мг/кг перорально. На восьмые сутки эксперимента у животных оценивали изменение массового коэффициента головного мозга, концентрации фосфорилированного тау-белка в мозговой ткани, активности цитохром-с-оксидазы и сукцинатдегирогеназы.</p> <p><bold>Результаты. </bold>Применение соединений Х3А4 и Х3А5 в равной степени с цитиколином уменьшало развитие тау-патологии, повышению активности митохондриальных ферментов: цитохром-с-оксидазы – на 14,5% (p&lt;0,05), 41,9% (p&lt;0,05) и 22,6% (p&lt;0,05) соответственно; сукцинатдегидрогеназы – на 28,6% (p&lt;0,05); 33,2% (p&lt;0,05) и 22,8% (p&lt;0,05) соответственно. В итоге на фоне введения животным указанных соединений и референта отмечено повышение массового коэффициента головного мозга по отношению к животным, не получавшим фармакологическую поддержку.</p> <p><bold>Заключение.</bold> Введение производных хромона Х3А4 и Х3А5 животным с экспериментальной хронической травматической энцефалопатией препятствует развитию тау-патологии и атрофии мозговой ткани, вероятно, за счет метаболического действия, выражающегося в восстановлении митохондриальной функции.</p></trans-abstract><kwd-group xml:lang="en"><kwd>tau protein</kwd><kwd>chromone derivatives</kwd><kwd>mitochondrial dysfunction</kwd><kwd>chronic traumatic encephalopathy</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>тау-белок</kwd><kwd>производные хромона</kwd><kwd>митохондриальная дисфункция</kwd><kwd>хроническая травматическая энцефалопатия</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Smith DH, Johnson VE, Trojanowski JQ, Stewart W. Chronic traumatic encephalopathy – confusion and controversies. Nat Rev Neurol. 2019;15(3):179-183. doi: 10.1038/s41582-018-0114-8</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(Pt 1):43-64. doi: 10.1093/brain/aws307</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Pourhadi N, Ringkøbing SP, Waldemar G, Frederiksen KS. Chronic traumatic encephalopathy. Ugeskr Laeger. 2021;183(23):V12200919</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Mez J, Daneshvar DH, Kiernan PT, et al. Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA. 2017;318(4):360-370. doi: 10.1001/jama.2017.8334</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Kulbe JR, Hall ED. Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology. Prog Neurobiol. 2017;158:15-44. doi: 10.1016/j.pneurobio.2017.08.003</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Höglinger GU, Lannuzel A, Khondiker ME, et al. The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy. J Neurochem. 2005;95(4):930-9. doi: 10.1111/j.1471-4159.2005.03493.x</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Kokjohn TA, Maarouf CL, Daugs ID, et al. Neurochemical profile of dementia pugilistica. J Neurotrauma. 2013;30:981-997.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Rukovitsyna VM, Pozdnyakov DI, Cheryapkin AS, Oganesyan ET. Derivatives of 3-formylchromone as modulators of mitochondrial complex III activity. Bulletin of the Voronezh State University. Series: Chemistry. Biology. Pharmacy. 2020;4:114-121. (In Russ.). [Руковицина В.М., Поздняков Д.И., Чиряпкин А.С., Оганесян Э.Т. Производные 3-формилхромона как модуляторы активности митохондриального комплекса III. Вестник Воронежского государственного университета. Серия: Химия. Биология. Фармация. 2020;4:114-121].</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Toklu HZ, Yang Z, Ersahin M, Wang KKW. Neurological Exam in Rats Following Stroke and Traumatic Brain Injury. Methods Mol Biol. 2019;2011:371-381. doi: 10.1007/978-1-4939-9554-7_21</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Abdolmaleki A, Moghimi A, Ghayour MB, Rassouli MB. Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats. Eur J Pharmacol. 2016;789:275-279. doi: 10.1016/j.ejphar.2016.07.048</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Li Y, D'Aurelio M, Deng JH. An assembled complex IV maintains the stability and activity of complex I in mammalian mitochondria. J Biol Chem. 2007; 24:17557-17562.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Wang H, Huwaimel B, Verma K. Synthesis and Antineoplastic Evaluation of Mitochondrial Complex II (Succinate Dehydrogenase) Inhibitors Derived from Atpenin A5. Chem Med Chem. 2017;12(13):1033-1044.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Jadhav S, Avila J, Schöll M, et al. A walk through tau therapeutic strategies. Acta Neuropathol Commun. 2019;7(1):22. doi: 10.1186/s40478-019-0664-z</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Gu H, Dodel R, Farlow MR, Du Y. Advances in the development of antibody-based immunotherapy against prion disease. Antibody Technology Journal. 2014;4:45-55 doi: 10.2147/ANTI.S53336</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Kabadi SV, Stoica BA, Byrnes KR, et al. Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma. J Cereb Blood Flow Metab. 2012;32(1):137-149. doi: 10.1038/jcbfm.2011.117</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Ng SY, Lee AYW. Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front Cell Neurosci. 2019;13:528. doi: 10.3389/fncel.2019.00528</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Lohr KM, Frost B, Scherzer C, Feany MB. Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model. Proc Natl Acad Sci USA. 2020;117(52):33608-33618. doi: 10.1073/pnas.1922392117</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Goldstein LE, Fisher AM, Tagge CA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med. 2012;4(134):134ra60. doi: 10.1126/scitranslmed.3003716</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Rak M, Bénit P, Chrétien D, et al. Mitochondrial cytochrome c oxidase deficiency. Clin Sci (Lond). 2016;130(6):393-407. doi: 10.1042/CS20150707</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Schumacker PT. Mitochondrial Succinate Dehydrogenase in Chronic Obstructive Pulmonary Disease: Is Complex II Too Complex? Am J Respir Cell Mol Biol. 2021;65(3):231-232. doi: 10.1165/rcmb.2021-0200ED</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Umemoto Y, Patel A, Huynh T, Chitravanshi VC. Wogonin attenuates the deleterious effects of traumatic brain injury in anesthetized Wistar rats. Eur J Pharmacol. 2019;848:121-130. doi: 10.1016/j.ejphar.2019.01.035</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Wang JW, Wang HD, Cong ZX, Zhou XM, Xu JG, Jia Y, Ding Y. Puerarin ameliorates oxidative stress in a rodent model of traumatic brain injury. J Surg Res. 2014;186(1):328-37. doi: 10.1016/j.jss.2013.08.027</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Segovia-Oropeza M, Santiago-Castañeda C, Orozco-Suárez SA, Concha L, Rocha L. Sodium Cromoglycate Decreases Sensorimotor Impairment and Hippocampal Alterations Induced by Severe Traumatic Brain Injury in Rats. J Neurotrauma. 2020;37(23):2595-2603. doi: 10.1089/neu.2019.6975</mixed-citation></ref></ref-list></back></article>
