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<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">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-ROL-2368</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-2368</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>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>Роль лейкоцитов в повреждении печени при моделировании сахарного диабета 1 и 2 типа</article-title><trans-title-group xml:lang="en"><trans-title>Role of leucocytes in liver damage in experimental models of type 1 and 2 diabetes mellitus</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5697-0370</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Байкенова</surname><given-names>М. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Baykenova</surname><given-names>M. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Байкенова Мадина Багатчановна – младший научный сотрудник ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук; аспирант ФГАОУ ВО «Уральский федеральный университет имени первого Президента России Б.Н. Ельцина»</p><p>620049, г. Екатеринбург, ул. Первомайская, 106</p></bio><bio xml:lang="en"><p>Baykenova Madina B., Junior Research Associate, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Science; Postgraduate Student,B. Yeltsin Ural Federal University</p><p>620049, Yekaterinburg, Pervomaiskaya str., 106</p></bio><email xlink:type="simple">m.b.baikenova@urfu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7024-4110</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Соколова</surname><given-names>К. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Sokolova</surname><given-names>K. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Соколова Ксения Викторовна – младший научный сотрудник</p><p>Екатеринбург</p></bio><bio xml:lang="en"><p>Junior Research Associate</p><p>Yekaterinburg</p></bio><email xlink:type="simple">kssocolova@bk.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3012-850X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гетте</surname><given-names>И. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Gette</surname><given-names>I. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гетте Ирина Федоровна – кандидат биологических наук , старший научный сотрудник</p><p>Екатеринбург</p></bio><bio xml:lang="en"><p>PhD (Biology), Senior Research Associate</p><p>Yekaterinburg</p></bio><email xlink:type="simple">i.goette@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6841-1197</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилова</surname><given-names>И. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilova</surname><given-names>I. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Данилова Ирина Георгиевна – доктор биологических наук, доцент, заведующая лабораторией морфологии и биохимии</p><p>Екатеринбург</p></bio><bio xml:lang="en"><p>PhD, MD (Biology), Associate Professor, Head, Laboratory of Morphology and Biochemistry</p><p>Yekaterinburg</p></bio><email xlink:type="simple">ig-danilova@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук;&#13;
ФГАОУ ВО «Уральский федеральный университет имени первого Президента России Б.Н. Ельцина»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Immunology and Physiology, Ural Branch, Russian Academy of Science;&#13;
B. Yeltsin Ural Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Immunology and Physiology, Ural Branch, Russian Academy of Science</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>B. Yeltsin Ural Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>20</day><month>04</month><year>2022</year></pub-date><volume>24</volume><issue>2</issue><fpage>263</fpage><lpage>272</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Байкенова М.Б., Соколова К.В., Гетте И.Ф., Данилова И.Г., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Байкенова М.Б., Соколова К.В., Гетте И.Ф., Данилова И.Г.</copyright-holder><copyright-holder xml:lang="en">Baykenova M.B., Sokolova K.V., Gette I.F., Danilova I.G.</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://www.mimmun.ru/mimmun/article/view/2368">https://www.mimmun.ru/mimmun/article/view/2368</self-uri><abstract><p>Сахарный диабет – это метаболическое расстройство, которое возникает в результате недостаточной секреции инсулина и/или его действия, что в результате приводит к возникновению гипергликемии. Известно, что поражение печени является одним из распространенных осложнений сахарного диабета 2 типа (СД2) и нередко встречается при диабете 1 типа (СД1). Сравнение распределения лейкоцитов с различным фенотипом в ткани печени с показателями крови может стать основой для диагностики степени поражения печени и поиска методов коррекции деструктивных изменений в печени при сахарном диабете. На основании вышеизложенного целью данного исследования была оценка изменения маркеров поражения печени в крови и количества лейкоцитов (CD45+ клеток), Т-лимфоцитов (CD3+ клеток) и макрофагов в печени при экспериментальном сахарном диабете 1 и 2 типа. Эксперимент был выполнен на 30 крысах-самцах линии Wistar. Для моделирования СД1 использовали аллоксан в дозе 170 мг/кг массы тела. Для создания модели СД2 животным вводили стрептозотоцин и никотинамид в дозах 65 мг/кг и 110 мг/кг. Группой сравнения служили интактные животные. Были выполнены биохимические, гематологические, иммуногистохимические и морфометрические методы исследования. При моделировании СД1 и СД2 были получены близкие значения содержания глюкозы (соответственно, 10,88±0,47 ммоль/л и 10,78±0,42 ммоль/л) и гликированного гемоглобина (соответственно, 6,73±0,78% и 6,60±0,20%), превышающие значения интактных крыс (5,20±0,40 ммоль/л и 4,07±0,30%). В то же время увеличение общего количество лейкоцитов и фракции лимфоцитов периферической крови относительно нормы было более выраженным в группе СД2, чем в группе СД1. В печени крыс обеих диабетических групп обнаружено увеличение количества синусоидальных клеток, макрофагов, CD45+ клеток и CD3+ клеток относительно показателей интактной группы, но у крыс группы СД1 CD45+ клетки располагались в большем количестве в паренхиме печени, а у крыс группы СД2 – синусоидально. При сходной степени увеличения количества макрофагов и общего количества CD45+ клеток, было выявлено более значительное количество синусоидальных клеток и CD3+ клеток, расположенных как в паренхиме, так и периваскулярно, у крыс группы СД2 по сравнению с показателем группы СД1. Увеличение активности АЛТ подтверждает более значительное повреждение клеток печени у животных группы СД2, тогда как в группе СД1 повышенная активность АСТ и менее выраженное увеличение активности АЛТ свидетельствуют о цитолизе без преимущественной локализации. Результаты исследования показали, что, несмотря на сходный уровень гипергликемии, воспалительный процесс на уровне целого организма и местный воспалительный процесс в печени более выражен в группе СД2, и более значительная выраженность воспалительного процесса и повреждения печени соответствует увеличению синусоидальных клеток и инфильтрации печени CD3+ клетками.</p><p> </p></abstract><trans-abstract xml:lang="en"><p>Diabetes mellitus is a metabolic disorder, which results from insufficient secretion of insulin and/or its action, thus leading to hyperglycemia. Liver damage is known to be among the most common complications of type 2 diabetes mellitus (T2D) and is common in T1D. Comparison of the leukocyte phenotypes in liver tissue with appropriate blood parameters may assess degree of liver damage and search for approaches to correction of liver destruction in diabetes mellitus. Therefore, we aimed for assessment of changes in liver injury markers in blood and the numbers of leucocytes (CD45+ cells), T lymphocytes (CD3+ cells) and macrophages in the liver in experimental models of types 1 and 2diabetes. The experiment was conducted on 30 male Wistar rats. Alloxan at the dose of 170 mg/kg of body weight was used for T1D modeling. To provide a model of T2D, streptozotocin and nicotinamide were injected at the doses of 65 mg/kg, and 110 mg/kg respectively. Intact animals were used as a comparison control. Biochemical, hematological, immunohistochemical and morphometrical methods were used in the study. In T1D and T2D groups, levels of glucose (10.88±0.47 mmol/l and 10.78±0.42 mmol/l) and glycosylated hemoglobin (6.73±0.78% and 6.60±0.20% correspondingly) were rather close to each other and exceeded the values of intact rats (5.20±0.40 mmol/l and 4.07±0.30%). At the same time, the increase in total leucocyte number and fraction of peripheral blood leucocytes against normal levels were more pronounced in the T2D group than in T2D group. In liver of rats from the both diabetic groups, increased numbers of sinusoidal cells, macrophages, CD45+ cells and CD3+ cells relative to intact rats were detected. However, in rats from T1D group, CD45+ cells were distributed, mainly, in the liver parenchyma, whereas in rats in T2D group they showed sinusoidal location. At a similar degree of increasing macrophage numbers, and total CD45+ cells number, higher counts of sinusoidal cells and CD3+ cells, located both in the parenchyma and perivascular area, were found in rats of T2DM group compared with this parameter in T1DM group. An increase in ALT activity confirms a more significant damage to liver cells in animals of the T2DM group, whereas, in T1DM group, an increased AST activity and a less pronounced increase in ALT activity indicate uniformly distributed cytolysis. The results of our study showed, that, despite similar hyperglycemia level, the inflammatory process at the level of the whole organism and local inflammatory process in the liver are more pronounced in the T2DM group. A more significant severity of inflammatory process and liver damage corresponds to increase in sinusoidal cells and CD3+ cell infiltration of liver tissue.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>сахарный диабет</kwd><kwd>печень</kwd><kwd>повреждение</kwd><kwd>лейкоциты</kwd><kwd>лимфоциты</kwd><kwd>макрофаги</kwd></kwd-group><kwd-group xml:lang="en"><kwd>diabetes mellitus</kwd><kwd>liver</kwd><kwd>damage</kwd><kwd>leukocytes</kwd><kwd>lymphocytes</kwd><kwd>macrophages</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">Балаболкин М.И., Клебанова Е.М., Креминская В.М. Лечение сахарного диабета и его осложнений (руководство для врачей). М.: Медицина, 2005. 512 с.</mixed-citation><mixed-citation xml:lang="en">Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Treatment of diabetes mellitus and its complications (a guide for doctors). Moscow: Meditsina, 2005. 512 p.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Данилова И.Г., Блинкова Н.Б., Гетте И.Ф., Пьянкова З.А., Белоусова А.В., Абидов М.Т. Влияние активации макрофагов на морфофункциональное состояние тучных клеток печени крыс с аллоксановым диабетом // Российский иммунологический журнал, 2016. Т. 10 (19), № 3. С. 244-246.</mixed-citation><mixed-citation xml:lang="en">Danilova I.G., Blinkova N.B., Gette I.F., Pyankova Z.A., Belousova A.V., Abidov M.T. The effect of macrophage activation on the morphofunctional state of liver mast cells in rats with alloxan diabetes. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2016, Vol. 10 (19), no. 3, pp. 244-246. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Данилова И.Г., Гетте И.Ф. Способ моделирования аллоксанового диабета. Патент на изобретение № 2534411; 2014.</mixed-citation><mixed-citation xml:lang="en">Danilova I.G., Gette I.F. Method for modeling alloxan diabetes. Patent RF. No. 2534411; 2014.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Журавлева Л.В. Огнева Е.В. Инсулиноподобный фактор роста-1, цитолиз и холестаз у больных неалкогольной жировой болезнью печени и при ее сочетании с сахарным диабетом 2-го типа // Клиницист, 2013. Т. 3, № 4. С. 48-52.</mixed-citation><mixed-citation xml:lang="en">Zhuravleva L.V. Ogneva E.V. Insulin-like growth factor-1, cytolysis and cholestasis in patients with non-alcoholic fatty liver disease and in its combination with type 2 diabetes mellitus. Klinitsist = Clinician, 2013, Vol. 3, no. 4, pp. 48-52. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Калмыкова З.А., Кононенко И.В., Майоров А.Ю. Сахарный диабет и хронические заболевания печени. Часть1: общие механизмы этиологии и патогенеза // Терапевтический архив, 2019. Т. 91, № 10. С. 106- 111.</mixed-citation><mixed-citation xml:lang="en">Kalmykova Z.A., Kononenko I.V., Mayorov A.Yu. Diabetes mellitus and chronic liver disease. Part 1: general mechanisms of etiology and pathogenesis. Terapevticheskiy arkhiv = Therapeutic Archive, 2019, Vol. 91, no. 10, pp. 106-111. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Петунина Н.А., Тельнова М.Э. Неалкогольная жировая болезнь печени при сахарном диабете 2-го типа // Медицинский совет, 2016. № 4. С. 92-95.</mixed-citation><mixed-citation xml:lang="en">Petunina N.A., Telnova M.E. Non-alcoholic fatty liver disease in type 2 diabetes mellitus. Meditsinskiy sovet = Medical Council, 2016, no. 4, pp. 92-95. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Спасов А.А., Воронкова М.П., Сингур Г.Л., Чепляева Н.И., Чепурнова М.В. Экспериментальная модель сахарного диабета типа 2 // Биомедицина, 2011. № 3. С. 12-18.</mixed-citation><mixed-citation xml:lang="en">Spassov A.A., Voronkova M.P., Singur G.L., Cheplyaeva N.I., Chepurnova M.V. Experimental model of diabetes mellitus type 2. Biomeditsina = Biomedicine, 2011, no. 3, pp. 12-18. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Шаронова Л.А., Вербовой А.Ф., Вербовая Н.И., Пашенцева А.В. Взаимосвязь неалкогольной жировой болезни печени и сахарного диабета 2-го типа // Русский медицинский журнал, 2017. № 22. С. 1635- 1640.</mixed-citation><mixed-citation xml:lang="en">Sharonova L.A., Verbovoy A.F., Verbovaya N.I., Pashentseva A.V. The relationship of non-alcoholic fatty liver disease and type 2 diabetes mellitus. Russkiy meditsinskiy zhurnal = Russian Medical Journal, 2017, no. 22, pp. 1635-1640. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bianchi E., Ripandelli G., Taurone S., Feher J., Plateroti R., Kovacs I., Magliulo G., Orlando M.P., Micera A., Battaglione E., Artico M. Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study. Int. J. Immunopathol. Pharmacol., 2016, Vol. 29, no. 1, pp. 40-53.</mixed-citation><mixed-citation xml:lang="en">Bianchi E., Ripandelli G., Taurone S., Feher J., Plateroti R., Kovacs I., Magliulo G., Orlando M.P., Micera A., Battaglione E., Artico M. Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study. Int. J. Immunopathol. Pharmacol., 2016, Vol. 29, no. 1, pp. 40-53.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Celik S., Erdogan S., Tuzcu M., Caffeic acid phenethyl ester (CAPE) exhibits significant potential as an antidiabetic and liver-protective agent in streptozotocin-induced diabetic rats. J. Pharmacol. Res., 2009, Vol. 60, no. 4, pp. 270-276.</mixed-citation><mixed-citation xml:lang="en">Celik S., Erdogan S., Tuzcu M., Caffeic acid phenethyl ester (CAPE) exhibits significant potential as an antidiabetic and liver-protective agent in streptozotocin-induced diabetic rats. J. Pharmacol. Res., 2009, Vol. 60, no. 4, pp. 270-276.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Cusi K., Sanyal A.J., Shuyu Zhang S., Hartman M.L., Bue-Valleskey J.M., Hoogwerf B.J., Haupt A. Nonalcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. J. Diabetes Obes. Metab., 2017, Vol 19, no. 11, pp. 1630-1634.</mixed-citation><mixed-citation xml:lang="en">Cusi K., Sanyal A.J., Shuyu Zhang S., Hartman M.L., Bue-Valleskey J.M., Hoogwerf B.J., Haupt A. Nonalcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. J. Diabetes Obes. Metab., 2017, Vol 19, no. 11, pp. 1630-1634.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Haidara M.A., Dallak M., El Karib A.O., Abd Ellatif M., Eid R.A., Heidar EH.A., Al-Ani B. Insulin protects against hepatocyte ultrastructural damage induced by type 1 diabetes mellitus in rats. J. Ultrastruct. Pathol., 2018, Vol. 42, no. 6, pp. 508-515.</mixed-citation><mixed-citation xml:lang="en">Haidara M.A., Dallak M., El Karib A.O., Abd Ellatif M., Eid R.A., Heidar EH.A., Al-Ani B. Insulin protects against hepatocyte ultrastructural damage induced by type 1 diabetes mellitus in rats. J. Ultrastruct. Pathol., 2018, Vol. 42, no. 6, pp. 508-515.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Kahraman N.K., Kahraman C., Koçak F.E., Coşgun S., Şanal B., Korkmaz M., Bayhan Z., Zeren S. Predictive value of neutrophiltolymphocyte ratio in the severity of non-alcoholic fatty liver disease among type 2 diabetes patients. J. Acta Gastroenterol. Belg., 2016, Vol. 79, no. 3, pp. 295-300.</mixed-citation><mixed-citation xml:lang="en">Kahraman N.K., Kahraman C., Koçak F.E., Coşgun S., Şanal B., Korkmaz M., Bayhan Z., Zeren S. Predictive value of neutrophiltolymphocyte ratio in the severity of non-alcoholic fatty liver disease among type 2 diabetes patients. J. Acta Gastroenterol. Belg., 2016, Vol. 79, no. 3, pp. 295-300.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Koyama Y., Brenner D. Liver inflammation and fibrosis. J. Clin. Invest., 2017, Vol. 127, no. 1, pp. 55-64.</mixed-citation><mixed-citation xml:lang="en">Koyama Y., Brenner D. Liver inflammation and fibrosis. J. Clin. Invest., 2017, Vol. 127, no. 1, pp. 55-64.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Masarone M., Rosato V., Aglitti A., Bucci T., Caruso R., Salvatore T., Sasso F.C., Tripodi M.F., Persico M. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage. PLoS One, 2017, Vol. 12, no. 6, e0178473. doi: 10.1371/journal.pone.0178473.</mixed-citation><mixed-citation xml:lang="en">Masarone M., Rosato V., Aglitti A., Bucci T., Caruso R., Salvatore T., Sasso F.C., Tripodi M.F., Persico M. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage. PLoS One, 2017, Vol. 12, no. 6, e0178473. doi: 10.1371/journal.pone.0178473.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Mendes-Braz M., Martins J.O. Diabetes mellitus and liver surgery: the effect of diabetes on oxidative stress and inflammation. Mediators Inflamm., 2018, Vol. 2018, pp. 1-11.</mixed-citation><mixed-citation xml:lang="en">Mendes-Braz M., Martins J.O. Diabetes mellitus and liver surgery: the effect of diabetes on oxidative stress and inflammation. Mediators Inflamm., 2018, Vol. 2018, pp. 1-11.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Robinson M.W., Harmon C., O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. J. Cell. Mol. Immunol., 2016, Vol. 13, no. 3, pp. 267-276.</mixed-citation><mixed-citation xml:lang="en">Robinson M.W., Harmon C., O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. J. Cell. Mol. Immunol., 2016, Vol. 13, no. 3, pp. 267-276.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Rodríguez V., Plavnik L., Talamoni N.T. Naringin attenuates liver damage in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2018, Vol. 105, pp. 95-102.</mixed-citation><mixed-citation xml:lang="en">Rodríguez V., Plavnik L., Talamoni N.T. Naringin attenuates liver damage in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2018, Vol. 105, pp. 95-102.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Romero-Zerbo S.Y., García-Fernández M., Espinosa-Jiménez V., Pozo-Morales M., Escamilla-Sánchez A., Sánchez-Salido L., Lara E., Cobo-Vuilleumier N., Rafacho A., Olveira G., Rojo-Martínez G., Gauthier B.R., González-Mariscal I., Bermúdez-Silva F.J. The atypical cannabinoid abn-CBD reduces inflammation and protects liver, pancreas, and adipose tissue in a mouse model of prediabetes and non-alcoholic fatty liver disease. Front. Endocrinol. (Lausanne), 2020, Vol. 11, no. 103, pp. 1-16</mixed-citation><mixed-citation xml:lang="en">Romero-Zerbo S.Y., García-Fernández M., Espinosa-Jiménez V., Pozo-Morales M., Escamilla-Sánchez A., Sánchez-Salido L., Lara E., Cobo-Vuilleumier N., Rafacho A., Olveira G., Rojo-Martínez G., Gauthier B.R., González-Mariscal I., Bermúdez-Silva F.J. The atypical cannabinoid abn-CBD reduces inflammation and protects liver, pancreas, and adipose tissue in a mouse model of prediabetes and non-alcoholic fatty liver disease. Front. Endocrinol. (Lausanne), 2020, Vol. 11, no. 103, pp. 1-16</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Sheweita S.A., Mashaly S. Newairy A.A., Abdou H.M., Eweda S.M. Changes in oxidative stress and antioxidant enzyme activities in streptozotocin-induced diabetes mellitus in rats: role of alhagi maurorum extracts. Oxid. Med. Cell. Longev., 2016, Vol. 2016, 5264064. doi: 10.1155/2016/5264064.</mixed-citation><mixed-citation xml:lang="en">Sheweita S.A., Mashaly S. Newairy A.A., Abdou H.M., Eweda S.M. Changes in oxidative stress and antioxidant enzyme activities in streptozotocin-induced diabetes mellitus in rats: role of alhagi maurorum extracts. Oxid. Med. Cell. Longev., 2016, Vol. 2016, 5264064. doi: 10.1155/2016/5264064.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Sanchez-Valle V., Chavez-Tapia N.C., Uribe M., Mendez-Sanchez N. Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr. Med. Chem., 2012, Vol. 19, no. 28, pp. 4850-4860.</mixed-citation><mixed-citation xml:lang="en">Sanchez-Valle V., Chavez-Tapia N.C., Uribe M., Mendez-Sanchez N. Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr. Med. Chem., 2012, Vol. 19, no. 28, pp. 4850-4860.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Shan Z., Cynthia J.C. Hepatic Macrophages in Liver Injury. Front. Immunol., 2020, Vol. 17, no. 11, 322. doi: 10.3389/fimmu.2020.00322.</mixed-citation><mixed-citation xml:lang="en">Shan Z., Cynthia J.C. Hepatic Macrophages in Liver Injury. Front. Immunol., 2020, Vol. 17, no. 11, 322. doi: 10.3389/fimmu.2020.00322.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Sviklāne L., Olmane E., Dzērve Z., Kupčs K., Pīrāgs V., Sokolovska J. Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes. J. Gastroenterol. Hepatol., 2018, Vol. 33, no. 1, pp. 270-276.</mixed-citation><mixed-citation xml:lang="en">Sviklāne L., Olmane E., Dzērve Z., Kupčs K., Pīrāgs V., Sokolovska J. Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes. J. Gastroenterol. Hepatol., 2018, Vol. 33, no. 1, pp. 270-276.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">van Herck M.A., Weyler J., Kwanten W.J., Dirinck E.L., De Winter B.Y., Francque S.M., Vonghia L. The differential roles of T cells in non-alcoholic fatty liver disease and obesity. Front. Immunol., 2019, Vol. 6, no. 10, 82. doi: 10.3389/fimmu.2019.00082.</mixed-citation><mixed-citation xml:lang="en">van Herck M.A., Weyler J., Kwanten W.J., Dirinck E.L., De Winter B.Y., Francque S.M., Vonghia L. The differential roles of T cells in non-alcoholic fatty liver disease and obesity. Front. Immunol., 2019, Vol. 6, no. 10, 82. doi: 10.3389/fimmu.2019.00082.</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>
