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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">sibmed</journal-id><journal-title-group><journal-title xml:lang="ru">Сибирский научный медицинский журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Сибирский научный медицинский журнал</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2410-2512</issn><issn pub-type="epub">2410-2520</issn><publisher><publisher-name>ИЦиГ СО РАН</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18699/SSMJ20240612</article-id><article-id custom-type="elpub" pub-id-type="custom">sibmed-1850</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>МЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOMEDICINE</subject></subj-group></article-categories><title-group><article-title>Оригинальный синтетический монофенольный антиоксидант комбинированного действия угнетает рост опухоли in vivo</article-title><trans-title-group xml:lang="en"><trans-title>Original synthetic monophenolic antioxidant with combined effect inhibits tumor growth in vivo</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2367-0114</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Меньщикова</surname><given-names>Е. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Menshchikova</surname><given-names>E. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Меньщикова Елена Брониславовна - д.м.н.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Elena B. Menshchikova - doctor of medical sciences.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">lemen7383@mail.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/0000-0003-3397-8067</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Храпова</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Khrapova</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Храпова Марина Валерьевна - к.б.н.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Marina V. Khrapova - candidate of biological sciences.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">marina.khrapova@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9989-9778</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кожин</surname><given-names>П. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Kozhin</surname><given-names>P. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кожин Петр Михайлович - к.м.н.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Peter M. Kozhin - candidate of medical sciences.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">kozhinpm@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0238-4533</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чечушков</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Chechushkov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Чечушков Антон Владимирович - к.м.н.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Anton V. Chechushkov - candidate of medical sciences.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">achechushkov@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7640-4867</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петрова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петрова Екатерина Сергеевна - к.х.н.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Ekaterina S. Petrova - candidate of chemical sciences.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">peteka2020@yandex.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/0000-0002-5817-6055</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Серых</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Serykh</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Серых Анастасия Евгеньевна.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Anastasia E. Serykh.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">rasiel1996@yandex.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/0009-0004-2054-3552</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ромах</surname><given-names>Л. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Romakh</surname><given-names>L. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ромах Лидия Петровна.</p><p>630117, Новосибирск, ул. Тимакова, 2</p></bio><bio xml:lang="en"><p>Lidiya P. Romakh.</p><p>630117, Novosibirsk, Timakova st., 2</p></bio><email xlink:type="simple">lpromakh@frcftm.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/0000-0001-6022-934X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кандалинцева</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kandalintseva</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандалинцева Наталья Валерьевна - д.х.н.</p><p>630126, Новосибирск, ул. Вилюйская, 28</p></bio><bio xml:lang="en"><p>Natalya V. Kandalintseva - doctor of chemical sciences.</p><p>630126, Novosibirsk, Vilyuyskaya st., 28</p></bio><email xlink:type="simple">aquaphenol@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФИЦ фундаментальной и трансляционной медицины</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Research Center of Fundamental and Translational Medicine</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Новосибирский государственный педагогический университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Pedagogical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>08</day><month>01</month><year>2025</year></pub-date><volume>44</volume><issue>6</issue><fpage>128</fpage><lpage>137</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Меньщикова Е.Б., Храпова М.В., Кожин П.М., Чечушков А.В., Петрова Е.С., Серых А.Е., Ромах Л.П., Кандалинцева Н.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Меньщикова Е.Б., Храпова М.В., Кожин П.М., Чечушков А.В., Петрова Е.С., Серых А.Е., Ромах Л.П., Кандалинцева Н.В.</copyright-holder><copyright-holder xml:lang="en">Menshchikova E.B., Khrapova M.V., Kozhin P.M., Chechushkov A.V., Petrova E.S., Serykh A.E., Romakh L.P., Kandalintseva N.V.</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://sibmed.elpub.ru/jour/article/view/1850">https://sibmed.elpub.ru/jour/article/view/1850</self-uri><abstract><p>Активированные кислородные метаболиты и антиоксиданты, так же как Аи редокс-чувствительный сигнальный Nrf2-зависимый путь, играют двойственную роль в формировании, росте и прогрессировании злокачественных новообразований. Целью настоящей работы послужило исследование способности оригинального синтетического монофенольного антиоксиданта комбинированного действия влиять на рост опухоли in vivo и на негативные эффекты применения цитостатика. Материал и методы. В качестве экспериментальной модели злокачественного роста использована карцинома легких Льюис (LLC). Исследование выполнено на 120 самках мышей линии C57Bl/6, которые были разделены на 12 групп; животных еженедельно взвешивали. Мыши соответствующих групп на протяжении всего эксперимента получали внутрижелудочно раствор оригинального монофенола 3-(3′-трет-бутил-4′-гидpокcифенил)пpопилтиоcульфоната натpия (ТС-13) (100 мг/кг массы тела), взвесь трет-бутилгидрохинона (tBHQ) либо растворителя (0,9%-й раствор NaCl). Через 28 дней после начала назначения ТС-13 и tBHQ мышам внутримышечно имплантировали взвесь клеток LLC в дозе 2×105 клеток/ мышь, на 7-й и 14-й день развития опухоли двукратно внутрибрюшинно вводили раствор доксорубицина в кумулятивной дозе 8 мг/кг массы тела (4/5 LD10). На 35-й день развития опухоли животных выводили из эксперимента, извлекали опухоль, взвешивали и определяли линейные размеры, вычисляли массовый коэффициент и объем опухоли. Также оценивали массовый коэффициент селезенки. Результаты и их обсуждение. На 7-й и 14-й день опухолевого роста масса тела животных, получавших ТС-13 и tBHQ, была статистически значимо больше, чем у остальных опухоленосителей. Назначение мышам ТС-13 так же эффективно, как и введение доксорубицина, угнетало рост опухоли, при комбинированном применении – более выраженно; tBHQ не оказывал самостоятельного ингибирующего действия, в комбинации с цитостатиком не усиливал его эффект. Доксорубицин существенно снижал массовый коэффициент селезенки, ТС-13 и tBHQ статистически значимо уменьшали эффект цитостатика. Монотерапия доксорубицином сопровождалась выпадением шерстяного покрова дорсальной поверхности (8 животных из 10), при совместном назначении цитостатика с ТС-13 и tBHQ алопеции не наблюдалось. Заключение. Монофенол ТС-13, прямой антиоксидант и индуктор системы Keap1/Nrf2/ARE, по выраженности противоопухолевого действия сопоставим с доксорубицином. Назначение ТС-13 позволяет существенно уменьшать негативные проявления, связанные со злокачественным ростом, и побочные эффекты химиотерапии, такие как кахексия, спленотоксичность, алопеция.</p></abstract><trans-abstract xml:lang="en"><p>Reactive oxygen metabolites and antioxidants, as well as the redox-sensitive signaling Nrf2-dependent pathway, play a dual role in the formation, growth and progression of malignant neoplasms. The aim of the study was to investigate the ability of the original synthetic monophenolic antioxidant of combined action to influence tumor growth in vivo and the side effects of cytostatic use. Material and methods. Lewis lung carcinoma (LLC) was used as an experimental model of malignant growth. The study was performed on 120 female C57Bl/6 mice, which were divided into 12 groups; the animals were weighed weekly. Mice of the corresponding groups received intragastrically a solution of sodium 3-(3′-tert-butyl-4′-hydroxyphenyl)propylthiosulfonate (TS-13) (100 mg/kg body weight), a suspension of tert-butylhydroquinone (tBHQ) or a solvent (0.9% NaCl solution) throughout the experiment. 28 days after the start of TS-13 and tBHQ administration, mice were implanted intramuscularly with a suspension of LLC cells at a dose of 2×105 cells/mouse; on the 7th and 14th days of tumor development, a solution of doxorubicin was administered intraperitoneally twice at a cumulative dose of 8 mg/kg body weight (4/5 LD10). On the 35th day of tumor growth, the animals were removed from the experiment, the tumor was extracted, weighed and its linear dimensions were determined; the tumor mass coefficient and volume were calculated, respectively. The spleen mass coefficient was also estimated. Results and discussion. On the 7th and 14th days of tumor growth, the body weight of animals receiving TS-13 and tBHQ was statistically significantly greater than that of other tumor carriers. Administration of TS-13 to mice inhibited tumor growth as effectively as doxorubicin, and more significantly when used in combination; tBHQ did not exert an independent inhibitory effect, and did not enhance its effect in combination with the cytostatic. Doxorubicin significantly reduced the spleen mass coefficient, while TS-13 and tBHQ statistically significantly reduced the effect of the cytostatic. Monotherapy with doxorubicin was accompanied by hair loss on the dorsal surface (8 animals out of 10), while no alopecia was observed with the combined administration of the cytostatic with TS-13 and tBHQ. Conclusions. Monophenol TS-13, a direct antioxidant and inducer of the Keap1/Nrf2/ARE system, is comparable to doxorubicin in terms of its antitumor effect. The use of TS-13 allows to significantly reduce the negative manifestations associated with malignant growth and the side effects of chemotherapy, such as cachexia, splenotoxity, and alopecia.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>карцинома легких Льюис</kwd><kwd>окислительный стресс</kwd><kwd>сигнальная система Keap1/Nrf2/ARE</kwd><kwd>доксорубицин</kwd><kwd>побочное действие цитостатиков</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Lewis lung carcinoma</kwd><kwd>oxidative stress</kwd><kwd>Keap1/Nrf2/ARE signaling system</kwd><kwd>doxorubicin</kwd><kwd>side effects of cytostatics</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена с использованием оборудования ЦКП «Современные оптические системы» и «Протеомный анализ», поддержанного финансированием Минобрнауки России (соглашение № 075-15-2021-691).</funding-statement><funding-statement xml:lang="en">The work was carried out using the equipment of the Center for Collective Use “Modern Optical Systems” and “Proteomic Analysis”, supported by funding from the Russian Ministry of Education and Science (agreement No. 075-15-2021-691).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Global cancer observatory. 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