<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">cardiovascular</journal-id><journal-title-group><journal-title xml:lang="ru">Кардиоваскулярная терапия и профилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Cardiovascular Therapy and Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1728-8800</issn><issn pub-type="epub">2619-0125</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">cardiovascular-1730</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНАЯ КАРДИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ЭКСПЕРИМЕНТАЛЬНАЯ КАРДИОЛОГИЯ</subject></subj-group></article-categories><title-group><article-title>Влияние триметазидина на энергетическую активность митохондрий</article-title><trans-title-group xml:lang="en"><trans-title>Trimetazidine effects on mitochondria energetic activity</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Елисеева</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Eliseeva</surname><given-names>S. V.</given-names></name></name-alternatives><email xlink:type="simple">astei@rinet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Грачев</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Grachev</surname><given-names>S. V.</given-names></name></name-alternatives><email xlink:type="simple">astei@rinet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Егорова</surname><given-names>Н. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Egorova</surname><given-names>N. D.</given-names></name></name-alternatives><email xlink:type="simple">astei@rinet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Глезер</surname><given-names>М. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Glezer</surname><given-names>M. G.</given-names></name></name-alternatives><email xlink:type="simple">astei@rinet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Асташкин</surname><given-names>Е. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Astashkin</surname><given-names>E. I.</given-names></name></name-alternatives><email xlink:type="simple">astei@rinet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Московская медицинская академия им. И.М.Сеченова. Москва</institution></aff><aff xml:lang="en"><institution>I.M. Sechenov Moscow Medical Academy. Moscow</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2008</year></pub-date><pub-date pub-type="epub"><day>20</day><month>12</month><year>2008</year></pub-date><volume>7</volume><issue>8</issue><fpage>64</fpage><lpage>69</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Елисеева С.В., Грачев С.В., Егорова Н.Д., Глезер М.Г., Асташкин Е.И., 2008</copyright-statement><copyright-year>2008</copyright-year><copyright-holder xml:lang="ru">Елисеева С.В., Грачев С.В., Егорова Н.Д., Глезер М.Г., Асташкин Е.И.</copyright-holder><copyright-holder xml:lang="en">Eliseeva S.V., Grachev S.V., Egorova N.D., Glezer M.G., Astashkin E.I.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://cardiovascular.elpub.ru/jour/article/view/1730">https://cardiovascular.elpub.ru/jour/article/view/1730</self-uri><abstract><sec><title>Цель</title><p>Цель. Изучить каким образом триметазидин (TMZ) оказывает непосредственное влияние на окислительное фосфорилирование интактных митохондрий (МХ), изолированных из животных, не подвергавшихся процессу ишемии-реперфузии.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Объектом исследования служили МХ печени крысы, выделяемые общепринятым методом. Окислительную и фосфорилирующую функции МХ изучали полярографически. TMZ использовали в концентрации 10-4М и 10-5М.</p></sec><sec><title>Результаты</title><p>Результаты. Под влиянием TMZ в концентрации 10-4М и 10-5М снизилось время фосфорилирования добавленного аденозиндифосфата (АДФ), уменьшилось количество кислорода (О2), для его фосфорилирования, в результате чего увеличился коэффициент АДФ/О. Такие изменения свидетельствуют о том, что увеличилась скорость процесса фосфорилирования и его эффективность, т. е. расходование О2 стало более экономным, а образование аденозинтрифосфата возросло. При воздействии TMZ увеличился дыхательный контроль, что также свидетельствует о повышении сопряженности процессов окисления и фосфорилирования. Показано, что сам по себе TMZ не вызывает разобщения этих процессов.</p></sec><sec><title>Заключение</title><p>Заключение. Улучшение энергетических функций МХ является одним из ключевых факторов в цитопротекторном действии TMZ.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. To investigate how trimetazidine (TMZ) directly affects oxidative phosphorylation in intact mitochondria (MCH), isolated from the animals not undergoing ischemia-reperfusion process.</p></sec><sec><title>Material and methods</title><p>Material and methods. Rat liver MCH were isolated by standard methods. Oxidative and phosphorylating MCH functions were studied by polarigraphic methods. TMZ was used in the concentrations of 10-4 М and 10-5 М.</p></sec><sec><title>Results</title><p>Results. TMZ in concentrations of 10-4 М and 10-5 М decreased the time of added adenosine diphosphate (ADPH) phosphorylation, reduced the amount of oxygen (O2) necessary for this phosphorylation, and increased ADPH/O2 coefficient. Therefore, phosphorylation velocity and effectiveness increased, i.e. O2 use became more economical, and ATPH synthesis increased. TMZ also increased breath control, which pointed to oxidation and phosphorylation association. TMZ per se did not separate these two processes.</p></sec><sec><title>Conclusion</title><p>Conclusion. MCH energetic function improvement is one of the key factors in TMZ cytoprotective effects.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>триметазидин</kwd><kwd>изолированные митохондрии</kwd><kwd>окисление и фосфорилирование</kwd></kwd-group><kwd-group xml:lang="en"><kwd>trimetazidine</kwd><kwd>isolated mitochondria</kwd><kwd>oxidation and phosphorylation</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Harpey C, Clauser P, Labrid C, et al. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Ddrug Rev 1989; 6: 292-312.</mixed-citation><mixed-citation xml:lang="en">Harpey C, Clauser P, Labrid C, et al. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Ddrug Rev 1989; 6: 292-312.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Renaud JF,. Internal pH, Na+ and Ca2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc drugs Ther 1988; 1(6): 677-86.</mixed-citation><mixed-citation xml:lang="en">Renaud JF,. Internal pH, Na+ and Ca2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc drugs Ther 1988; 1(6): 677-86.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Cruz C, Zaoui A, Ayoub S, et al. Alterations des myocytes isoles des ventricules de coeur de rat adulte: Protection par la trimetazidine. Concours Med 1987; 36(Suppl): 3470-5.</mixed-citation><mixed-citation xml:lang="en">Cruz C, Zaoui A, Ayoub S, et al. Alterations des myocytes isoles des ventricules de coeur de rat adulte: Protection par la trimetazidine. Concours Med 1987; 36(Suppl): 3470-5.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Tsimoyiannis EC, Moutesidou KJ, Moschos CM, et al. Trimetazidine for prevention of hepatic injury induced by ischemia and reperfusion in rats. Eur J Surg 1993; 159: 89-93.</mixed-citation><mixed-citation xml:lang="en">Tsimoyiannis EC, Moutesidou KJ, Moschos CM, et al. Trimetazidine for prevention of hepatic injury induced by ischemia and reperfusion in rats. Eur J Surg 1993; 159: 89-93.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Guarnieri C, Muscari C. Effectof trimetazidine on mitochondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium. Pharmacology 1993; 46: 324-31.</mixed-citation><mixed-citation xml:lang="en">Guarnieri C, Muscari C. Effectof trimetazidine on mitochondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium. Pharmacology 1993; 46: 324-31.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Elimadi A, Settaf A, Morin D, et al. Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion by preserving mitochondrial function. J Pharmacol Exp Ther 1998;</mixed-citation><mixed-citation xml:lang="en">Elimadi A, Settaf A, Morin D, et al. Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion by preserving mitochondrial function. J Pharmacol Exp Ther 1998;</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Elimadi A, Morin D, Sapena R, et al. Comparison of the effects of cyclosporine A and trimetazidine on Ca2+-dependent mitochondrial swelling. Fundam Clin Pharmacol 1997; 11: 440-7.</mixed-citation><mixed-citation xml:lang="en">Elimadi A, Morin D, Sapena R, et al. Comparison of the effects of cyclosporine A and trimetazidine on Ca2+-dependent mitochondrial swelling. Fundam Clin Pharmacol 1997; 11: 440-7.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Salducci MD, Chauvet-Monges AM, Tillement JP, et al. Trimetazidine reverses calcium accumulation and impairment of phosphorylation induced by cyclosporine A in isolated rat liver mitochondria. J Pharmacol Exp Ther 1996; 277: 417-22.</mixed-citation><mixed-citation xml:lang="en">Salducci MD, Chauvet-Monges AM, Tillement JP, et al. Trimetazidine reverses calcium accumulation and impairment of phosphorylation induced by cyclosporine A in isolated rat liver mitochondria. J Pharmacol Exp Ther 1996; 277: 417-22.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Tillement JP, Crevat A, Testa B, Le Ridant A. Pharmacological modulation of mitochondrial oxidative phosphorylation: inhibition by cyclosporine A, restoration by trimetazidine. Ann Pharm Fr 1996; 54(6): 268-71.</mixed-citation><mixed-citation xml:lang="en">Tillement JP, Crevat A, Testa B, Le Ridant A. Pharmacological modulation of mitochondrial oxidative phosphorylation: inhibition by cyclosporine A, restoration by trimetazidine. Ann Pharm Fr 1996; 54(6): 268-71.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Morin D, Elimadi A, Sapena R, et al. Evidence for the existence of [-3H]-trimetazidine binding sites involved in the regulation of the mitochondrial permeability transition pore. Brit J Pharmacol 1998; 123: 1385-94.</mixed-citation><mixed-citation xml:lang="en">Morin D, Elimadi A, Sapena R, et al. Evidence for the existence of [-3H]-trimetazidine binding sites involved in the regulation of the mitochondrial permeability transition pore. Brit J Pharmacol 1998; 123: 1385-94.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Morin D, Sapena R, Elimadi A, et al. [3H]-trimetazidine mitochondrial binding sites: regulation by cations, effect of trimetazidine derivatives and other agents and interaction with an endogenous substance. Brit J Pharmacol 2000; 130: 655-63.</mixed-citation><mixed-citation xml:lang="en">Morin D, Sapena R, Elimadi A, et al. [3H]-trimetazidine mitochondrial binding sites: regulation by cations, effect of trimetazidine derivatives and other agents and interaction with an endogenous substance. Brit J Pharmacol 2000; 130: 655-63.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Schneider WC, Hogeboom GH. Intracellular distribution of enzymes. J Biol Chem 1950; 183: 123.11.</mixed-citation><mixed-citation xml:lang="en">Schneider WC, Hogeboom GH. Intracellular distribution of enzymes. J Biol Chem 1950; 183: 123.11.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Гублер Е.В., Генкин А.А. Применение непараметрических критериев статистики в медико-биологических исследованиях. Ленинград "Медицина" 1973; 141 с: 12.</mixed-citation><mixed-citation xml:lang="en">Гублер Е.В., Генкин А.А. Применение непараметрических критериев статистики в медико-биологических исследованиях. Ленинград "Медицина" 1973; 141 с: 12.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Grynberg A, Demaison L. Fatty acid oxidation in the heart. J Cardiovasc Pharmacol 1996; 28(Suppl 1): Sl 1-7.</mixed-citation><mixed-citation xml:lang="en">Grynberg A, Demaison L. Fatty acid oxidation in the heart. J Cardiovasc Pharmacol 1996; 28(Suppl 1): Sl 1-7.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">GrynbergA. Effectors offatty acid oxidation reduction: promising new anti-ischaemic agents. Curr Pharmaceutical Design 2005; 11(4): 489-509.</mixed-citation><mixed-citation xml:lang="en">GrynbergA. Effectors offatty acid oxidation reduction: promising new anti-ischaemic agents. Curr Pharmaceutical Design 2005; 11(4): 489-509.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Essop MF, Opie LH. Metabolic therapy for heart failure. Eur Heart J 2004; 25: 1765-8.</mixed-citation><mixed-citation xml:lang="en">Essop MF, Opie LH. Metabolic therapy for heart failure. Eur Heart J 2004; 25: 1765-8.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol 2003; 17(2): 133-45.</mixed-citation><mixed-citation xml:lang="en">Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol 2003; 17(2): 133-45.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580-8.</mixed-citation><mixed-citation xml:lang="en">Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580-8.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Асташкин Е.И., Глезер М.Г. Фармакологическая регуляция обмена энергетических субстратов в кардиомиоцитах при патологических состояниях, связанных с ишемией. Кардиоваск тер профил 2006; 5(7): 112-23.</mixed-citation><mixed-citation xml:lang="en">Асташкин Е.И., Глезер М.Г. Фармакологическая регуляция обмена энергетических субстратов в кардиомиоцитах при патологических состояниях, связанных с ишемией. Кардиоваск тер профил 2006; 5(7): 112-23.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Tabbi-Anneni I, Lucien A, Grynberg A. Trimetazidine effect on phospholipid synthesis in ventricular myocytes: consequence in p-adrenergic dignaling. Fundam Clin Pharmacol 2003; 17: 51-9.</mixed-citation><mixed-citation xml:lang="en">Tabbi-Anneni I, Lucien A, Grynberg A. Trimetazidine effect on phospholipid synthesis in ventricular myocytes: consequence in p-adrenergic dignaling. Fundam Clin Pharmacol 2003; 17: 51-9.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Argaud L, Gomez L, Gateau-Roesch O, et al. Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury. J Mol Cell Cardiol 2005; 39(6): 893-9.</mixed-citation><mixed-citation xml:lang="en">Argaud L, Gomez L, Gateau-Roesch O, et al. Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury. J Mol Cell Cardiol 2005; 39(6): 893-9.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Morillas Blasco PJ, Hernandiz Martinez A, Azorin Villena I, et al. Mitochondrial changes induced by trimetazidine in the myocardium. Med Sci Monit 2005; 11(6): BR 162-7.</mixed-citation><mixed-citation xml:lang="en">Morillas Blasco PJ, Hernandiz Martinez A, Azorin Villena I, et al. Mitochondrial changes induced by trimetazidine in the myocardium. Med Sci Monit 2005; 11(6): BR 162-7.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Maridonneau-Parini I, Harpey C. Trimetazidine protects the human red blood cell against oxygen free radical damage. Cardiovasc Drugs Ther 1990; 4: 818-9.</mixed-citation><mixed-citation xml:lang="en">Maridonneau-Parini I, Harpey C. Trimetazidine protects the human red blood cell against oxygen free radical damage. Cardiovasc Drugs Ther 1990; 4: 818-9.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
