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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">medlit</journal-id><journal-title-group><journal-title xml:lang="ru">Гигиена и санитария</journal-title><trans-title-group xml:lang="en"><trans-title>Hygiene and Sanitation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0016-9900</issn><issn pub-type="epub">2412-0650</issn><publisher><publisher-name>Federal Scientific Center of Hygiene named after F.F. Erisman</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47470/0016-9900-2024-103-5-407-415</article-id><article-id custom-type="edn" pub-id-type="custom">acuahh</article-id><article-id custom-type="elpub" pub-id-type="custom">medlit-4043</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>ГИГИЕНА ОКРУЖАЮЩЕЙ СРЕДЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ENVIRONMENTAL HYGIENE</subject></subj-group></article-categories><title-group><article-title>Прогноз вероятных негативных эффектов, инициированных трансформацией протеомного профиля плазмы крови человека при комбинированном воздействии химических веществ</article-title><trans-title-group xml:lang="en"><trans-title>Forecast of probable negative effects initiated by transformation of the proteomic profile of human blood plasma under combined exposure to chemicals</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2356-1145</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зайцева</surname><given-names>Нина Владимировна</given-names></name><name name-style="western" xml:lang="en"><surname>Zaitseva</surname><given-names>Nina V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Академик РАН, доктор мед. наук, профессор, науч. руководитель ФБУН «ФНЦ медико-профилактических технологий управления рисками здоровью населения», 614045, Пермь, Россия.</p><p>e-mail: znv@fcrisk.ru</p></bio><bio xml:lang="en"><p>MD, PhD, Dsci, professor, Academician of the RAS, Scientific Head of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation; Russian Academy of Sciences, Department of Medical Sciences (Section of Preventive Medicine), Moscow, 119071, Russian Federation</p><p>e-mail: znv@fcrisk.ru</p></bio><email xlink:type="simple">znv@fcrisk.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/0000-0002-8013-9613</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Землянова</surname><given-names>Марина Александровна</given-names></name><name name-style="western" xml:lang="en"><surname>Zemlyanova</surname><given-names>Marina A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор мед. наук, доцент, зав. отд. биохимических и цитогенетических методов диагностики ФБУН «ФНЦ медико-профилактических технологий управления рисками здоровью населения», 614045, Пермь</p><p>e-mail: zem@fcrisk.ru</p></bio><bio xml:lang="en"><p>MD, PhD, Dsci., Associate Professor, Head of the Department of biochemical and cytogenetic diagnostic methods of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation, Perm State National Research University, Perm, 614990, Russian Federation</p><p>e-mail: zem@fcrisk.ru</p></bio><email xlink:type="simple">zem@fcrisk.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/0000-0002-8050-3059</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пескова</surname><given-names>Екатерина Владимировна</given-names></name><name name-style="western" xml:lang="en"><surname>Peskova</surname><given-names>Ekaterina V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мл. науч. сотр. отд. биохимических и цитогенетических методов диагностики ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения», аспирант ФБУН «ФНЦ медико-профилактических технологий управления рисками здоровью населения», 614045, Пермь</p><p>e-mail: peskova@fcrisk.ru</p></bio><bio xml:lang="en"><p>Postgraduate student, junior researcher, Department of biochemical and cytogenetic diagnostic methods of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation</p><p>e-mail: peskova@fcrisk.ru</p></bio><email xlink:type="simple">peskova@fcrisk.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека; ФГБУ «Российская академия наук»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Scientific Center for Medical and Preventive Health Risk Management Technologies; Russian Academy of Sciences, Department of Medical Sciences (Section of Preventive Medicine)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека; ФГБОУ ВО «Пермский государственный национальный исследовательский университет»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Scientific Center for Medical and Preventive Health Risk Management Technologies; Perm State National Research University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Scientific Center for Medical and Preventive Health Risk Management Technologies</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>17</day><month>06</month><year>2024</year></pub-date><volume>103</volume><issue>5</issue><fpage>407</fpage><lpage>415</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Зайцева Н.В., Землянова М.А., Пескова Е.В., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Зайцева Н.В., Землянова М.А., Пескова Е.В.</copyright-holder><copyright-holder xml:lang="en">Zaitseva N.V., Zemlyanova M.A., Peskova E.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://www.rjhas.ru/jour/article/view/4043">https://www.rjhas.ru/jour/article/view/4043</self-uri><abstract><sec><title>Введение</title><p>Введение. Исследование механизмов внешнесредового воздействия химических веществ на организм человека с помощью высокоинформативных технологий протеомного профилирования позволяет прогнозировать развитие негативных эффектов на самой ранней стадии их формирования. В сочетании с экспериментальными исследованиями, исключающими влияние мешающих факторов, повышается точность идентификации изменений белкового профиля. Оценка причинно-следственных связей воздействия химических веществ с преобразованием белков повышает эффективность прогноза и мер профилактики негативных последствий.</p><p>Цель исследования — прогноз вероятных негативных эффектов, инициированных трансформацией протеомного профиля плазмы крови при комбинированном воздействии химических веществ, на основе биоинформационных матриц по результатам сопоставительного анализа натурных и экспериментальных исследований (на примере оксида алюминия, фторида водорода и бенз(а)пирена).</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Методами химико-аналитического, статистического, протеомного и биоинформационного анализа проведено распознавание молекулярно-клеточных событий у детей 4–7 лет, подвергающихся аэрогенной экспозиции бенз(а)пиреном, фторидом водорода и оксидом алюминия (натурные исследования). В ходе сопоставительного анализа проведена верификация полученных результатов данными экспериментальных исследований (крысы линии Wistar), подвергающихся комбинированной и изолированной ингаляционной экспозиции в дозах, эквивалентных реальным. Выделены тождественные белки и построена биоинформационная матрица, на основе которой с использованием общепризнанных баз метаданных выполнен прогноз вероятных негативных эффектов.</p></sec><sec><title>Результаты</title><p>Результаты. В результате натурных исследований установлено, что у детей, экспонированных бенз(а)пиреном на уровне до 2,2 ПДКс.г. (до 2,2 RfC), оксидом алюминия и фторидом водорода до 0,3 ПДКс.г. (до 0,1 RfC), концентрации изучаемых веществ в биосредах в 2–3,6 раза превышали показатели сравнения и референтные уровни. В эксперименте у экспонированных животных содержание данных контаминантов в биосредах до 19,4 раза превышало показатели контроля. У детей выявлено 22 белка, соответствующих библиотечным масс-спектрам, у животных — 40 белков. При сопоставительном анализе белков, идентифицированных в плазме крови детей и крыс, выделены аполипопротеин A-I и транстиретин, оценённые как «тождественные». Экспрессия данных белков увеличивается с повышением концентрации изучаемых веществ в биосредах. Согласно информации из баз данных, повышенная экспрессия аполипопротеина A-I и транстиретина сигнализирует об увеличении риска возникновения окислительного стресса, нарушения метаболизма липидов и развития воспалительных процессов. Построена биоинформационная матрица, позволившая прогнозировать метаболические нарушения, преимущественно в тканях нервной и гепатобилиарной систем.</p></sec><sec><title>Ограничения исследования</title><p>Ограничения исследования. Проведённое исследование не позволяет сделать окончательных выводов о влиянии изучаемых веществ на изменение экспрессии белков и кодирующих их генов, поскольку рассмотрен только аэрогенный путь поступления.</p></sec><sec><title>Заключение</title><p>Заключение. Установлена трансформация протеомного профиля плазмы крови в натурных исследованиях и экспериментально верифицированная при хроническом ингаляционном воздействии оксида алюминия, фторида водорода и бенз(а)пирена. При сопоставительном анализе идентифицированных белков выявлено два тождественных — аполипопротеин A-I и транстиретин. Построена биоинформационная матрица и выполнен прогноз развития негативных эффектов в виде активации окислительных процессов, дисметаболизма липидов и воспаления, метаболический путь которых связан с изменением экспрессии данных белков. При отсутствии мер профилактики это может обусловить в старшем возрастном периоде развитие атеросклероза, гипертонии, ожирения, амилоидоза, гипертиреоза и др. Использование структурных биоинформационных матриц в качестве инструмента прогноза в гигиенических исследованиях повышает эффективность мер направленной профилактики негативных последствий при внешнесредовом воздействии химических веществ.</p><p>Соблюдение этических стандартов. Экспериментальные исследования на биологической модели проведены с соблюдением требований Европейской конвенции по защите позвоночных животных, используемых для экспериментальных или в иных научных целях (ETS № 123). Обследование детей выполнено с соблюдением этических принципов Хельсинкской декларации (2013 г.). Исследования одобрены Комитетом по биомедицинской этике ФБУН «ФНЦ МПТ УРЗН» (протокол заседания № 1 от 4.02.2021 г.).</p></sec><sec><title>Участие авторов</title><p>Участие авторов:Зайцева Н.В. — редактирование;Землянова М.А. — концепция и дизайн исследования, редактирование;Пескова Е.В. — концепция и дизайн исследования, сбор данных литературы, статистическая обработка материала, написание текста.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.</p></sec><sec><title>Конфликт интересов</title><p>Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.</p></sec><sec><title>Финансирование</title><p>Финансирование. Исследование выполнено за счёт средств Федерального бюджета.</p></sec><sec><title>Поступила</title><p>Поступила: 16.02.2024 / Поступила после доработки: 13.03.2024 / Принята к печати: 09.04.2024 / Опубликована: 17.06.2024</p></sec><sec><title> </title><p> </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. The study of the mechanisms of external environmental effects of chemicals on the human body using highly informative proteomic profiling technologies makes it possible to predict the development of negative effects at the earliest stage of their formation. In combination with experimental studies that exclude the influence of interfering factors, the accuracy of identifying changes in the protein profile increases. Assessing the cause-and-effect relationships between exposure to chemicals and protein transformation increases the effectiveness of prognosis and measures to prevent negative consequences.</p><p>The purpose of the work is the forecast of probable negative effects initiated by the transformation of the proteomic profile of blood plasma under the combined influence of chemicals, relied upon on bioinformation matrices based on the results of a comparative analysis of natural and experimental studies (using the example of aluminum oxide, hydrogen fluoride, and benzo(a)pyrene).</p></sec><sec><title>Materials and methods</title><p>Materials and methods. Using the methods of chemical-analytical, statistical, proteomic, and bioinformational analysis, molecular-cellular events were identified in 4–7 years children exposed to aerogenic exposure to benzo(a)pyrene, hydrogen fluoride, and aluminum oxide (field studies). During the comparative analysis, the obtained results were verified by data from experimental studies (Wistar rats) subjected to combined and isolated inhalation exposure in doses equivalent to real ones. Identical proteins were identified and a bioinformation matrix was constructed, on the basis of which a forecast of probable negative effects was made using generally accepted metadata databases.</p></sec><sec><title>Results</title><p>Results. As a result of field studies, in children exposed to benzo(a)pyrene at a level of up to 2.2 MPC.g. (up to 2.2 RfC), aluminum oxide and hydrogen fluoride — up to 0.3 MPC.g. (up to 0.1 RfC), the concentrations of the studied substances in biological media were established to be 2.0–3.6 times higher than the comparison indicators and reference levels. In the experiment, the content of these contaminants in biological media in exposed animals was up to 19.4 times higher than in the control. In children there were identified, 22 proteins corresponding to the library mass spectra, 40 proteins — in animals. In a comparative analysis of proteins identified in the blood plasma in children and rats, Apolipoprotein A-I and Transthyretin were identified and assessed as “identical”. The expression of these proteins elevates with increasing concentration of the studied substances in biological media. According to information from databases, increased expression of Apolipoprotein A-I and Transthyretin signals an higher risk for the oxidative stress, impaired lipid metabolism, and the development of inflammatory processes. The constructed bioinformation matrix made it possible to predict metabolic disorders, mainly in the tissues of the nervous and hepatobiliary systems.</p></sec><sec><title>Limitations</title><p>Limitations. The study does not allow drawing definitive conclusions about the effect of the studied chemicals on changes in the expression of proteins and the genes encoding them, since in this work only the aerogenic route of entry is considered.</p></sec><sec><title>Conclusion</title><p>Conclusion. The transformation of the proteomic profile of blood plasma was established in field studies and experimentally verified during chronic inhalation exposure to aluminum oxide, hydrogen fluoride and benzo(a)pyrene. A comparative analysis of the identified proteins revealed two identical ones — Apolipoprotein A-I and Transthyretin. A bioinformation matrix was constructed and a forecast was made for the development of negative effects in the form of activation of oxidative processes, lipid dysmetabolism and inflammation, the metabolic pathway of which is associated with changes in the expression of these proteins. In the absence of preventive measures, this can lead to the development of atherosclerosis, hypertension, obesity, amyloidosis, hyperthyroidism, etc. in older age. The use of structural bioinformation matrices as a forecasting tool in hygienic research increases the effectiveness of targeted prevention measures for negative consequences due to environmental exposure to chemicals.</p><p>Compliance with ethical standards. Experimental studies on a biological model were conducted in compliance with the requirements of the European Convention for the Protection of Vertebrates Used for Experimental or Other Scientific Purposes (ETS No. 123). The examination of children was carried out in compliance with the ethical principles of the Helsinki Declaration (2013). The research was approved by the Committee on Biomedical Ethics of the Federal State Budgetary Institution “FNC MPT URZN” (minutes of meeting No. 1 dated 02/14/2021).</p></sec><sec><title>Contribution</title><p>Contribution: Zaitseva N.V. — editing;Zemlyanova M.A. — concept and design of research, editing;Peskova E.V. — concept and design of research, collection of literature data, statistical processing of material, writing of text.All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version</p></sec><sec><title>Conflict of interest</title><p>Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest in connection with the publication of this article.</p></sec><sec><title>Acknowledgement</title><p>Acknowledgement. The study was carried out at the expense of the Federal budget.</p></sec><sec><title>Received</title><p>Received: February 16, 2024 / Revised: March 13, 2024 / Accepted: April 9, 2024 / Published: June 17, 2024</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>протеомный профиль</kwd><kwd>биологическая модель</kwd><kwd>комбинированная экспозиция</kwd><kwd>контаминация биосред</kwd><kwd>биоинформационный анализ</kwd><kwd>негативные эффекты</kwd><kwd>прогнозные оценки</kwd><kwd>здоровье человека</kwd></kwd-group><kwd-group xml:lang="en"><kwd>proteomic profile</kwd><kwd>biological model</kwd><kwd>combined exposure</kwd><kwd>contamination of biological media</kwd><kwd>bioinformation analysis</kwd><kwd>negative effects</kwd><kwd>predictive estimates</kwd><kwd>human health</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">Skinner M.K. 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