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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">safetyrisk</journal-id><journal-title-group><journal-title xml:lang="ru">Безопасность и риск фармакотерапии</journal-title><trans-title-group xml:lang="en"><trans-title>Safety and Risk of Pharmacotherapy</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2312-7821</issn><issn pub-type="epub">2619-1164</issn><publisher><publisher-name>Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/2312-7821-2023-11-3-303-321</article-id><article-id custom-type="elpub" pub-id-type="custom">safetyrisk-373</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>ОТ ИССЛЕДОВАНИЙ IN VITRO К КЛИНИЧЕСКИМ ИССЛЕДОВАНИЯМ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>FROM IN VITRO EXPERIMENTS TO CLINICAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Применение зебраданио (zebrafish) в доклинических исследованиях лекарственных средств: проблемы и перспективы</article-title><trans-title-group xml:lang="en"><trans-title>Using Zebrafish in Preclinical Drug Studies: Challenges and Opportunities</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7525-1950</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Калуев</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kalueff</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Калуев Алан Валерьевич - доктор биологических наук, профессор РАН.</p><p>Олимпийский пр-т, д. 1, пгт. Сириус, Краснодарский край, 354340; ул. Аккуратова, д. 2, Санкт-Петербург, 197341; Университетская наб., д. 7–9, Санкт-Петербург, 199034; ул. Ленинградская, д. 70, п. Песочный, Санкт-Петербург, 197758</p></bio><bio xml:lang="en"><p>Allan V. Kalueff - Dr. Sci. (Biol.), Professor of the Russian Academy of Sciences.</p><p>Olimpiyskiy Ave, Sirius urban-type settlement Krasnodar region 354340; Akkuratova St., St Petersburg 197341; 7–9 Universitetskaya Emb., St Petersburg 199034; 70 Leningradskaya St., Pesochny settlement, St Petersburg 197758</p></bio><email xlink:type="simple">avkalueff@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/0000-0002-9287-1115</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Котова</surname><given-names>М. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotova</surname><given-names>M. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Котова Мария Михайловна.</p><p>Олимпийский пр-т, д. 1, пгт. Сириус, Краснодарский край, 354340</p></bio><bio xml:lang="en"><p>Maria M. Kotova</p><p>Olimpiyskiy Ave, Sirius urban-type settlement Krasnodar region 354340</p></bio><email xlink:type="simple">kotova.maria522@yandex.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/0000-0002-5191-0974</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Икрин</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Ikrin</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Икрин Алексей Николаевич.</p><p>Олимпийский пр-т, д. 1, пгт. Сириус, Краснодарский край, 354340</p></bio><bio xml:lang="en"><p>Aleksey N. Ikrin</p><p>Olimpiyskiy Ave, Sirius urban-type settlement Krasnodar region 354340</p></bio><email xlink:type="simple">ikrin00@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5561-8583</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колесникова</surname><given-names>Т. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolesnikova</surname><given-names>T. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Колесникова Татьяна Олеговна</p><p>Олимпийский пр-т, д. 1, пгт. Сириус, Краснодарский край, 354340</p></bio><bio xml:lang="en"><p>Tatiana O. Kolesnikova</p><p>Olimpiyskiy Ave, Sirius urban-type settlement Krasnodar region 354340</p></bio><email xlink:type="simple">philimontani@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Автономная некоммерческая образовательная организация высшего образования «Научно-технологический университет «Сириус»; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В.А. Алмазова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»; Федеральное государственное бюджетное учреждение «Российский научный центр радиологии и хирургических технологий имени академика А.М. Гранова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Sirius University of Science and Technology; Almazov National Medical Research Center; St Petersburg State University; A.M. Granov Russian Research Center for Radiology and Surgical Technologies</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Автономная некоммерческая образовательная организация высшего образования «Научно-технологический университет «Сириус»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Sirius University of Science and Technology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>26</day><month>09</month><year>2023</year></pub-date><volume>11</volume><issue>3</issue><fpage>303</fpage><lpage>321</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Калуев А.В., Котова М.М., Икрин А.Н., Колесникова Т.О., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Калуев А.В., Котова М.М., Икрин А.Н., Колесникова Т.О.</copyright-holder><copyright-holder xml:lang="en">Kalueff A.V., Kotova M.M., Ikrin A.N., Kolesnikova T.O.</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.risksafety.ru/jour/article/view/373">https://www.risksafety.ru/jour/article/view/373</self-uri><abstract><sec><title>Актуальность</title><p>Актуальность. В доклинических испытаниях лекарственных средств становится актуальным применение вспомогательных водных позвоночных моделей, в частности рыб зебраданио (zebrafish, Danio rerio), поскольку использование грызунов для биоскрининга лекарственных препаратов существенно ограничивают фискальная и регуляторная нагрузки.</p></sec><sec><title>Цель</title><p>Цель. Анализ эффективности модели зебраданио в доклинических исследованиях лекарственных средств, а также обзор текущего состояния ее использования, проблем и перспектив в этой области и определение стратегических направлений дальнейшего развития доклинического тестирования на зебраданио.</p></sec><sec><title>Обсуждение</title><p>Обсуждение. В работе описаны основные тесты на зебраданио, используемые для оценки общей токсичности, выживаемости эмбрионов и личинок, а также эндокринных нарушений, для широкого спектра малых молекул. Выявлены преимущества и недостатки применения зебраданио в доклинических испытаниях нейротропных соединений. Обозначены методологические подходы повышения эффективности токсикологических исследований препаратов на зебраданио. Показано, что в целом использование зебраданио постепенно закрепляется в качестве одного из этапов тестирования малых молекул в лабораториях мира.</p></sec><sec><title>Выводы</title><p>Выводы. Широкое внедрение данного модельного организма в исследовательскую и доклиническую практику в качестве дополнительного (вспомогательного) теста помимо исследований на грызунах позволит существенно ускорить разработку новых лекарственных препаратов, а также более полно и адекватно оценивать биологические риски воздействия химических веществ.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Scientific relevance</title><p>Scientific relevance. Since fiscal and regulatory constraints substantially limit bioscreening in rodent models, a wider implementation of additional alternative models in preclinical studies of medicines is gaining momentum. These alternative models include aquatic vertebrates, such as zebrafish (Danio rerio).</p></sec><sec><title>Aim</title><p>Aim. The study aimed to examine zebrafish models in terms of their performance in preclinical studies, their current uses, the challenges and opportunities in the field, and strategic directions for the development of preclinical testing in zebrafish.</p></sec><sec><title>Discussion</title><p>Discussion. Here, the authors summarise the key zebrafish tests that are currently used to assess a wide range of small molecules for their general and endocrine toxicity and effects on the survival of embryos and larvae. The review discusses the strengths and weaknesses of zebrafish models for preclinical testing of neurotropic agents. Additionally, the authors overview various methodological approaches to improving zebrafish toxicity testing. Overall, the use of zebrafish models is gradually becoming internationally established for laboratory testing of small molecules.</p></sec><sec><title>Conclusions</title><p>Conclusions. A wider implementation of zebrafish models in pharmaceutical research and preclinical testing as an additional alternative to rodents, particularly in Russia, may significantly accelerate the development of novel medicinal products and foster a more comprehensive and adequate assessment of the biological risks associated with chemical substances.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>доклинические исследования</kwd><kwd>токсикологические исследования</kwd><kwd>зебраданио</kwd><kwd>Danio rerio</kwd><kwd>лекарственные препараты</kwd><kwd>биоскрининг</kwd></kwd-group><kwd-group xml:lang="en"><kwd>preclinical studies</kwd><kwd>toxicology studies</kwd><kwd>zebrafish</kwd><kwd>Danio rerio</kwd><kwd>medicinal products</kwd><kwd>bioscreening</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа поддержана средствами Научно-технологического университета «Сириус» (субсидия Министерства науки и высшего образования Российской Федерации, соглашение № 075-10-2021-093). Работа А.В. Калуева также финансово поддержана Санкт-Петербургским государственным университетом (проект № 93020614)</funding-statement><funding-statement xml:lang="en">The study was supported by the Sirius University of Science and Technology (subsidy from the Ministry of Science and Higher Education of the Russian Federation, Agreement No. 075-10-2021-093). A.V. Kalueff’s work was also funded by St Petersburg State University (Project No. 93020614)</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">Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, et al. Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat Rev Drug Discov. 2014;13(6):419–31. https://doi.org/10.1038/nrd4309</mixed-citation><mixed-citation xml:lang="en">Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, et al. 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