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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">RUDN Journal of Medicine</journal-id><journal-title-group><journal-title xml:lang="en">RUDN Journal of Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник Российского университета дружбы народов. Серия: Медицина</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-0245</issn><issn publication-format="electronic">2313-0261</issn><publisher><publisher-name xml:lang="en">Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">25024</article-id><article-id pub-id-type="doi">10.22363/2313-0245-2020-24-4-293-303</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>EXPERIMENTAL PHYSIOLOGY</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНАЯ ФИЗИОЛОГИЯ</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">Optimum marker selection of acute liver damage in rats in the experiment</article-title><trans-title-group xml:lang="ru"><trans-title>Выбор оптимального маркера острого повреждения печени крыс в эксперименте</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="spin">9456-9710</contrib-id><name-alternatives><name xml:lang="en"><surname>Popov</surname><given-names>K. A.</given-names></name><name xml:lang="ru"><surname>Попов</surname><given-names>К. А.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="spin">4493-0738</contrib-id><name-alternatives><name xml:lang="en"><surname>Tsymbalyuk</surname><given-names>I. Y.</given-names></name><name xml:lang="ru"><surname>Цымбалюк</surname><given-names>И. Ю.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="spin">6921-7356</contrib-id><name-alternatives><name xml:lang="en"><surname>Sepiashvili</surname><given-names>R. I.</given-names></name><name xml:lang="ru"><surname>Сепиашвили</surname><given-names>Р. И.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="spin">9977-6613</contrib-id><name-alternatives><name xml:lang="en"><surname>Bykov</surname><given-names>I. M.</given-names></name><name xml:lang="ru"><surname>Быков</surname><given-names>И. М.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ustinova</surname><given-names>E. S.</given-names></name><name xml:lang="ru"><surname>Устинова</surname><given-names>Е. С.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="spin">2909-3520</contrib-id><name-alternatives><name xml:lang="en"><surname>Bykov</surname><given-names>M. I.</given-names></name><name xml:lang="ru"><surname>Быков</surname><given-names>М. И.</given-names></name></name-alternatives><email>naftalin444@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Kuban State Medical University</institution></aff><aff><institution xml:lang="ru">Кубанский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Peoples’ Friendship University of Russia (RUDN University)</institution></aff><aff><institution xml:lang="ru">Российский университет дружбы народов</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2020-12-15" publication-format="electronic"><day>15</day><month>12</month><year>2020</year></pub-date><volume>24</volume><issue>4</issue><issue-title xml:lang="en">EXPERIMENTAL AND CLINICAL  PHYSIOLOGY</issue-title><issue-title xml:lang="ru">ЭКСПЕРИМЕНТАЛЬНАЯ И КЛИНИЧЕСКАЯ ФИЗИОЛОГИЯ</issue-title><fpage>293</fpage><lpage>303</lpage><history><date date-type="received" iso-8601-date="2020-11-23"><day>23</day><month>11</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2020, Popov K.A., Tsymbalyuk I.Y., Sepiashvili R.I., Bykov I.M., Ustinova E.S., Bykov M.I.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2020, Попов К.А., Цымбалюк И.Ю., Сепиашвили Р.И., Быков И.М., Устинова Е.С., Быков М.И.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="en">Popov K.A., Tsymbalyuk I.Y., Sepiashvili R.I., Bykov I.M., Ustinova E.S., Bykov M.I.</copyright-holder><copyright-holder xml:lang="ru">Попов К.А., Цымбалюк И.Ю., Сепиашвили Р.И., Быков И.М., Устинова Е.С., Быков М.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/">http://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.rudn.ru/medicine/article/view/25024">https://journals.rudn.ru/medicine/article/view/25024</self-uri><abstract xml:lang="en"><p style="text-align: justify;"><italic>Relevance</italic>. Assessment of liver damage and functional state is one of the leading tasks of clinical and laboratory diagnostics. Traditionally used methods for determining the activity of a number of indicator enzymes in blood with relative organ-specificity, such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, sorbitol dehydrogenase, alkaline phosphatase, and γ-glutamyl transferase, have low specificity for liver diseases. In this regard, the determination of the optimal marker of acute liver injury is an urgent problem. <italic>Aim. </italic>The purpose of the study is to determine the dynamics of changes in liver damage markers in rats at different periods of reperfusion after 20 minutes of ischemia in order to select the indicators that most informatively characterize the state of test-animals under conditions of correction of ischemia-reperfusion syndrome. <italic>Materials and methods: </italic>the study was performed on 120 white nonlinear male rats weighing 200–250 grams. The animals were divided into 8 groups of 15 test-animals; all of them were simulated liver ischemia by clamping the analog of the hepatoduodenal ligament with a vascular clamp for 20 minutes. Then, blood was taken from different groups of rats at different reperfusion times – 5, 15, 30, 60, 120, 180 minutes, 8 hours and a day. In the blood plasma of laboratory animals, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione transferase (GST), and lactate concentration were determined. <italic>Results: </italic>the results obtained allowed us to characterize two main peaks of indicators: a 5-minute period after restoration of blood flow – the maximum activity of glutathione transferase and lactate concentration, increased by 3.9–4.7 times; 60–180 minutes of reperfusion is the peak of aminotransferase activity, a significant increase in the activity of which begins 60 minutes after the restoration of blood flow and reaches its maximum by the 3rd hour of reperfusion, and LDH, the peak of which is recorded already by the 60th minute of revascularization. At the same time, after 8 hours of reperfusion, an obvious tendency for a decrease in all studied parameters was determined, which ends a day after modeling ischemia with a decrease to the level of control values. <italic>Conclusion: </italic>the assessment of organ damage in the ischemic period and the anti-ischemic effect of metabolic drugs can be carried out with the determination of an increase in lactate concentration and glutathione transferase activity almost immediately after restoration of blood flow. The development of injuries during the reperfusion period is more expedient to assess by determining AST, ALT and LDH after a 3-hour period of blood flow restoration, at which time the maximum values of markers are recorded under the condition of 20-minute total liver ischemia.</p></abstract><trans-abstract xml:lang="ru"><p class="s43" style="text-align: justify; text-indent: 14.2pt; margin: 0cm 11.9pt .0001pt 7.1pt;">Актуальность. <span class="s151">Оценка повреждения и функционального состояния печени является одной из ведущих задач клинико-лабораторной диагностики. Традиционно используемые методы определения в крови активности ряда индикаторных ферментов, обладающих относительной органоспецифичностью, таких как аспартатаминотрансфераза, аланинаминотрансфераза, лактатдегидрогеназа, сорбитолдегидрогеназа, щелочная фосфатаза и γ-глутамилтрансфераза обладают низкой их специфичностью по отношению к заболеваниям печени. В связи с этим определение оптимального маркера острого повреждения печени является актуальной проблемой. </span>Цель: <span class="s151">определение динамики изменений маркеров повреждения печени у крыс на разных сроках реперфузии после 20-ти минутной ишемии для выбора показателей, наиболее информативно характеризующих состояние животных в условиях проведения коррекции ишемически-реперфузионного синдрома. </span>Материалы и методы: <span class="s151">исследование проведено на 120 белых нелинейных крысах-самцах массой 200–250 грамм. Животные были разделены на 8 групп по 15 особей, всем животным выполнялось моделирование ишемии печени путем пережатия аналога печеночно-двенадцатиперстной связки сосудистым зажимом на 20 минут. Затем у разных групп крыс производили забор крови в разные сроки реперфузии – 5, 15, 30, 60, 120, 180 минут, 8 часов и сутки. В плазме крови лабораторных животных определяли активность аланинаминотрансферазы (АЛТ), аспартатаминотрансферазы (АСТ), лактатдегидрогеназы (ЛДГ), глутатионтрансферазы (ГSТ) и концентрацию лактата. </span>Результаты: <span class="s151">полученные результаты позволили охарактеризовать два основных пика показателей: 5-минутный период после восстановления кровотока – максимум активности глутатионтрансферазы и концентрации лактата, увеличенных в 3,9–4,7 раза; 60–180 минут реперфузии – пик активности аминотрансфераз, значительный рост активности которых начинается с 60-ти минут после восстановления кровотока и достигает максимума к 3-му часу реперфузии, и ЛДГ, пик активности которой регистрируется уже к 60-й минуте реваскуляризации. При этом через 8 часов реперфузии определена очевидная тенденция снижения всех изученных показателей, которая заканчивается спустя сутки после моделирова</span>ния ишемии снижением до уровня контрольных значений. <italic>Заключение: </italic>оценка повреждения органа в ишемическом периоде и противоишемического действия метаболических препаратов может проводиться с определением нарастания концентрации лактата и активности глутатионтрансферазы практически сразу после восстановления кровотока. Развитие повреждений в реперфузионный период более целесообразно оценивать путем определения АСТ, АЛТ и ЛДГ после 3-часового периода восстановления кровотока, в это время регистрируются максимальные значения маркеров при условии 20-минутной тотальной ишемии печени.</p></trans-abstract><kwd-group xml:lang="en"><kwd>liver</kwd><kwd>ischemia</kwd><kwd>reperfusion</kwd><kwd>cytolysis</kwd><kwd>hepatocytes</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>печень</kwd><kwd>ишемия</kwd><kwd>реперфузия</kwd><kwd>цитолиз</kwd><kwd>гепатоциты</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The study was carried out as part of the state assignment of the Ministry of Health of the Russian Federation № АААА-А18–118122690052–3.</funding-statement><funding-statement xml:lang="ru">Исследование выполнено в рамках государственного задания Министерства здравоохранения Российской Федерации № АААА-А18–118122690052–3.</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Voloshchuk O., Kopylchuk G. Serum sorbitol dehydrogenase activity as a sensitive marker of liver damage. Laboratory diagnostics. Eastern Europe. 2015;2(14):94–99. (In Russ).</mixed-citation><mixed-citation xml:lang="ru">Волощук О.Н., Копыльчук Г.П. Активность сорбитолдегидрогеназы сыворотки как чувствительный маркер повреждения печени // Лабораторная диагностика. Восточная Европа. 2015. № 2 (14). С. 94-99.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">Tsymbalyuk I.Y., Manuilov A.M., Popov K.A., Basov A.A. Metabolic correction of the ischemia-reperfusive injury with sodium dichloroacetate in vascular isolation of the liver in experiment. Novosti Khirurgii. 2017;25(5):447–453. doi: 10.18484/2305– 0047.2017.5.447. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Цымбалюк И.Ю., Мануйлов А.М., Попов К.А., Басов А.А. Метаболическая коррекция дихлорацетатом натрия ишемически-реперфузионного повреждения при сосудистой изоляции печени в эксперименте // Новости хирургии. 2017. 25 (5). С. 447-453. doi: 10.18484/2305-0047.2017.5.447.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">Saidi R.F., Kenari S.K. Liver ischemia/reperfusion injury: an overview. J. Invest. Surg. 2014;27(6):366–379. doi:10.3109/089 41939.2014.932473.</mixed-citation><mixed-citation xml:lang="ru">Saidi R.F., Kenari S.K. Liver ischemia/reperfusion injury: an overview // J. Invest. Surg. 2014. V. 27 (6). P. 366-379. doi:10.3109/08941939.2014.932473.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">Liang J., Zhou Y., Wang Z., Chen H. Relationship between liver damage and serum levels of IL-18, TNF-alpha and NO in patients with acute pancreatitis. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30(8):1912–1914.</mixed-citation><mixed-citation xml:lang="ru">Liang J., Zhou Y., Wang Z., Chen H. Relationship between liver damage and serum levels of IL-18, TNF-alpha and NO in patients with acute pancreatitis // Nan Fang Yi Ke Da Xue Xue Bao. 2010. V. 30 (8). P. 1912-1914.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">Basov A.A., Elkina А.A., Samkov A.A., Volchenko N.N., Baryshev M.G., Dzhimak S.S., et al. Influence of deuteriumdepleted water on the isotope D/H composition of liver tissue and morphological development of rats at different periods of ontogenesis. Iranian Biomedical Journal. 2019;23(2):129–141.</mixed-citation><mixed-citation xml:lang="ru">Basov A.A., Elkina А.A., Samkov A.A., Volchenko N.N., Baryshev M.G., Dzhimak S.S., et al. Influence of deuteriumdepleted water on the isotope D/H composition of liver tissue and morphological development of rats at different periods of ontogenesis // Iranian Biomedical Journal. 2019. V. 23. № 2. P. 129-141.</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">Johansen M.J., Gade J., Stender S., Frithioff-Bøjsøe C., Lund M AV., Chabanova E., et al. The effect of overweight and obesity on liver biochemical markers in children and adolescents. J. Clin. Endocrinol. Metab. 2020;105(2): dgz010. doi:10.1210/clinem/ dgz010.</mixed-citation><mixed-citation xml:lang="ru">Johansen M.J., Gade J., Stender S., Frithioff-Bøjsøe C., Lund M. AV., Chabanova E., et al. The effect of overweight and obesity on liver biochemical markers in children and adolescents // J. Clin. Endocrinol. Metab. 2020. V. 105 (2). dgz010. doi:10.1210/ clinem/dgz010.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">Dzidzava I.I., Slobodyanik A.V., Kudryavtseva A.V., Zheleznyak I.S., Kotiv B.N., Alentyev S.A., et al. The results of СТ-volumetry and clearance test with indocyanine green as indications for preoperative portal vein embolization. Annals of HPB surgery. 2016;21(3):34–46. (In Russ).</mixed-citation><mixed-citation xml:lang="ru">Дзидзава И.И., Слободяник А.В., Кудрявцева А.В., Железняк И.С., Котив Б.Н., Алентьев С.А., и др. Применение КТ-волюметрии и клиренс-теста с индоцианином зеленым для определения показаний к предоперационной эмболизации воротной вены // Анналы хирургической гепатологии. 2016. Т. 21 (3). С. 34-46.</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">Halle B.M., Poulsen T.D., Pedersen H.P. Indocyanine green plasma disappearance rate as dynamic liver function test in critically ill patients. Acta Anaesthesiol Scand. 2014;58(10):1214–1219. doi:10.1111/aas.12406.</mixed-citation><mixed-citation xml:lang="ru">Halle B.M., Poulsen T.D., Pedersen H.P. Indocyanine green plasma disappearance rate as dynamic liver function test in critically ill patients // Acta Anaesthesiol. Scand. 2014. V. 58 (10). P. 1214-1219. doi:10.1111/aas.12406.</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">Sakka S.G. Assessment of liver perfusion and function by indocyanine green in the perioperative setting and in critically ill patients. J. Clin. Monit. Comput. 2018;32(5):787–796. doi:10.1007/ s10877–017–0073–4.</mixed-citation><mixed-citation xml:lang="ru">Sakka S.G. Assessment of liver perfusion and function by indocyanine green in the perioperative setting and in critically ill patients // J. Clin. Monit. Comput. 2018. V. 32 (5). P. 787-796. doi: 10.1007/s10877-017-0073-4.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Dzhimak S.S., Basov A.A., Volchenko N.N., Samkov A.A., Baryshev M.G., Fedulova L.V. Changes in the functional activity of mitochondria isolated from the liver of rat that passed the preadaptation to ultra-low deuterium concentration. Doklady Biochemistry and Biophysics. 2017;476(1):323–325.</mixed-citation><mixed-citation xml:lang="ru">Dzhimak S.S., Basov A.A., Volchenko N.N., Samkov A.A., Baryshev M.G., Fedulova L.V. Changes in the functional activity of mitochondria isolated from the liver of rat that passed the preadaptation to ultra-low deuterium concentration // Doklady Biochemistry and Biophysics. 2017. V. 476. № 1. P. 323-325.</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">Ge Y., Zhang Q., Jiao Z., Li H., Bai G., Wang H. Adipose-derived stem cells reduce liver oxidative stress and autophagy induced by ischemia-reperfusion and hepatectomy injury in swine. Life Sci. 2018;214:62–69. doi:10.1016/j.lfs.2018.10.054.</mixed-citation><mixed-citation xml:lang="ru">Ge Y., Zhang Q., Jiao Z., Li H., Bai G., Wang H. Adipose-derived stem cells reduce liver oxidative stress and autophagy induced by ischemia-reperfusion and hepatectomy injury in swine // Life Sci. 2018. V. 214. P. 62-69. doi:10.1016/j.lfs.2018.10.054.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">Karpishchenko A.I. Handbook. Medical Laboratory Technology. Sankt-Petersburg: Intermedika, 2002. (In Russ).</mixed-citation><mixed-citation xml:lang="ru">Карпищенко А.И. Медицинские лабораторные технологии. Справочник. СПб: Интермедика, 2002. 600 с.</mixed-citation></citation-alternatives></ref></ref-list></back></article>
