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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">10.47470/0016-9900-2025-104-11-1452-1457</article-id><article-id custom-type="edn" pub-id-type="custom">jowetz</article-id><article-id custom-type="elpub" pub-id-type="custom">medlit-5292</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 ДЕТЕЙ И ПОДРОСТКОВ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>HYGIENE OF CHILDREN AND ADOLESCENTS</subject></subj-group></article-categories><title-group><article-title>Особенности показателей нейромедиаторной регуляции у школьников с расстройствами вегетативной нервной системы в условиях полиморфизма генов ApoE Cys130Arg и SIRT1 C&gt;G и биоэкспозиции тяжёлыми металлами</article-title><trans-title-group xml:lang="en"><trans-title>Features of indices of neurotransmitter regulation in schoolchildren with disorders of the autonomic nervous system under conditions of polymorphism of the ApoE Cys130Arg and SIRT1 C&gt;G genes and bioexposure to heavy metals</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 МПТ УРЗН», 614045, Пермь, Россия</p><p>e-mail: znv@fcrisk.ru</p></bio><bio xml:lang="en"><p>DSc (Medicine), professor, academician of the RAS, scientific director of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, 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/0000-0002-6173-6017</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Отавина</surname><given-names>Елена Алексеевна</given-names></name><name name-style="western" xml:lang="en"><surname>Otavina</surname><given-names>Elena A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мл. науч. сотр. лаб. иммуногенетики отд. иммунобиологических методов диагностики ФБУН «ФНЦ МПТ УРЗН», 614045, Пермь, Россия</p><p>e-mail: eleninca@mail.ru</p></bio><bio xml:lang="en"><p>Junior researcher, Laboratory of immunogenetics, Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation</p><p>e-mail: eleninca@mail.ru</p></bio><email xlink:type="simple">eleninca@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/0000-0003-4860-3145</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Долгих</surname><given-names>Олег Владимирович</given-names></name><name name-style="western" xml:lang="en"><surname>Dolgikh</surname><given-names>Oleg V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор мед. наук, зав. отд. иммунобиологических методов диагностики ФБУН «ФНЦ МПТ УРЗН», 614045, Пермь, Россия</p><p>e-mail: oleg@fcrisk.ru</p></bio><bio xml:lang="en"><p>DSc (Medicine), head, Department of immunobiological diagnostic methods, Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation</p><p>e-mail: oleg@fcrisk.ru</p></bio><email xlink:type="simple">oleg@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/0000-0002-0114-3930</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Казакова</surname><given-names>Ольга Алексеевна</given-names></name><name name-style="western" xml:lang="en"><surname>Kazakova</surname><given-names>Olga A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Канд. биол. наук, ст. науч. сотр., зав. лаб. иммуногенетики ФБУН «ФНЦ МПТ УРЗН», 614045, Пермь, Россия</p><p>e-mail: chakina2011@yandex.ru</p></bio><bio xml:lang="en"><p>PhD (Biology), senior researcher, head, Immunogenetics Laboratory, Department of immunobiological diagnostic methods, Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation</p><p>e-mail: chakina2011@yandex.ru</p></bio><email xlink:type="simple">chakina2011@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения» Роспотребнадзора</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>2025</year></pub-date><pub-date pub-type="epub"><day>19</day><month>12</month><year>2025</year></pub-date><volume>104</volume><issue>11</issue><fpage>1452</fpage><lpage>1457</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Зайцева Н.В., Отавина Е.А., Долгих О.В., Казакова О.А., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Зайцева Н.В., Отавина Е.А., Долгих О.В., Казакова О.А.</copyright-holder><copyright-holder xml:lang="en">Zaitseva N.V., Otavina E.A., Dolgikh O.V., Kazakova O.A.</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/5292">https://www.rjhas.ru/jour/article/view/5292</self-uri><abstract><sec><title>Введение</title><p>Введение. Значительный вклад в распространение расстройств вегетативной нервной системы (ВНС) вносит химическое загрязнение окружающей среды тяжёлыми металлами (ТМ). В современной диагностике и профилактике нарушений здоровья, сопряжённых с качеством среды обитания, перспективным направлением является идентификация полиморфизмов кандидатных генов, ассоциированных с риском развития расстройств ВНС.</p><p>Цель исследования – оценка особенностей показателей нейромедиаторной регуляции у школьников-подростков с расстройством вегетативной нервной системы в условиях полиморфных вариантов генов АpoE, SIRT1 и контаминации крови кадмием, свинцом, мышьяком.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Обследованы 633 школьника, проживающих в условиях низкоуровневой аэрогенной экспозиции ТМ (до 1 ПДКс.г.), из них 330 с расстройствами ВНС (G90.8–G90.9) и 303 условно здоровых (группа сравнения). Выполнена оценка полиморфизмов генов ApoE (rs429358), SIRT1 (rs7069102) методом ПЦР, уровня контаминантов в крови методом масс-спектрометрии с индуктивно связанной плазмой, показателей нейроиммуногенеза методом ИФА.</p></sec><sec><title>Результаты</title><p>Результаты. Школьники с патологией ВНС имеют повышенное содержание кадмия, свинца и мышьяка в крови, повышение частоты С-аллели и ТС-генотипа гена ApoE (rs429358), а также С-аллели гена SIRT1 (rs7069102) (RR = 1,23–1,83) относительно группы сравнения. Установлено достоверное повышение экспрессии нейроиммуномедиаторов ацетилхолина и адреналина (в 1,2 раза) и пониженный уровень экспрессии лептина и интерлейкина-17А (в 1,4–1,5 раза) по сравнению с показателями здоровых детей.</p><p>Ограничения исследования определяются используемыми показателями эффекта.</p></sec><sec><title>Заключение</title><p>Заключение. Установленные особенности полиморфизма генов ApoE (rs429358), SIRT1 (rs7069102) у детей отражают риск формирования расстройств ВНС в условиях низкоуровневой аэрогенной экспозиции ТМ. Показатели нейромедиаторной регуляции, С-аллель генов ApoE (rs429358) и SIRT1 (rs7069102) рекомендуется использовать в качестве индикаторных для задач профилактики и снижения риска развития болезней ВНС у школьников-подростков в условиях избыточной биоэкспозиции кадмием, свинцом, мышьяком.</p><p>Соблюдение этических стандартов. Исследование одобрено этическим комитетом ФБУН ФНЦ МПТ УРЗН (протокол № 14 от 14.03.2023 г.). Все участники и их законные представители дали информированное добровольное письменное согласие на участие в исследовании.</p></sec><sec><title>Участие авторов</title><p>Участие авторов: Зайцева Н.В. – дизайн исследования, редактирование; Отавина Е.А. – сбор и обработка материала, статистическая обработка, написание и редактирование текста; Долгих О.В. – концепция, дизайн исследования, редактирование; Казакова О.А. – сбор и обработка материала, статистическая обработка, редактирование. Все соавторы – утверждение окончательного варианта статьи, ответственность за целостность всех её частей.</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 не имело спонсорской поддержки.</p></sec><sec><title>Поступила</title><p>Поступила: 04.09.2025 / Принята к печати: 15.10.2025 / Опубликована: 19.12.2025</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. An increasing chemical pollution of the environment with heavy metals (HMs) makes a significant contribution to the spread of disorders of the autonomic nervous system (ANS). In modern diagnostics and prevention of health disorders associated with the quality of the environment, a promising direction is the identification of polymorphisms of candidate genes associated with the risk of developing ANS diseases.</p></sec><sec><title>The aim of the study</title><p>The aim of the study. To evaluate the characteristics of neurotransmitter regulation in adolescent schoolchildren with ANS disorders under conditions of polymorphic variants of the ApoE, SIRT1 genes and blood contamination with cadmium, lead, and arsenic. </p></sec><sec><title>Materials and methods</title><p>Materials and methods. Six hundred thirty three schoolchildren living in conditions of low-level aerogenic HM exposure (up to 1 average annual MAC) were examined, 330 of them with ANS disorders (G90.8–G90.9) and 303 conditionally healthy (comparison group). Polymorphisms of the ApoE (rs429358), SIRT1 (rs7069102) genes were evaluated by PCR, the level of contaminants in the blood by inductively coupled plasma mass spectrometry, and neuroimmunogenesis parameters by ELISA.</p></sec><sec><title>Results</title><p>Results. Schoolchildren with ANS pathology are characterized by an increased blood content of cadmium, lead, and arsenic, an elevation of the frequency of the C-allele and TC-genotype of the ApoE gene (rs429358), as well as the C-allele of the SIRT1 gene (rs7069102) (RR=1.23–1.83) relative to the comparison group. There was a significant increase in the expression of neuroimmunomediators acetylcholine and adrenaline (1.2 times) and a decreased expression of leptin and interleukin-17A (1.4–1.5 times) in relation to the indicators in healthy children. </p></sec><sec><title>Limitations</title><p>Limitations. The limited range of effect indicators used in this study.</p></sec><sec><title>Conclusion</title><p>Conclusion. The established polymorphism features of ApoE (rs429358), SIRT1 (rs7069102) genes in children reflect the risk of ANS disorders in conditions of low-level aerogenic HMs exposure. Indicators of neurotransmitter regulation, the C-allele of the ApoE (rs429358) and SIRT1 (rs7069102) genes are recommended to be used as indicators for the prevention and reduction of the risk of developing ANS diseases in adolescent schoolchildren under conditions of excessive bioexposure to cadmium, lead, and arsenic.</p><p>Compliance with ethical standards. The study was approved by the ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (Protocol No.14 of 14/03/2023). All participants and their legal representatives gave informed voluntary written consent to participate in the study.</p></sec><sec><title>Contribution</title><p>Contribution: Zaitseva N.V. — research design, editing; Otavina E.A. — collection and processing of material, statistical processing, writing and editing of text; Dolgikh O.V. — concept, research design, editing; Kazakova O.A. — collection and processing of material, statistical processing, editing. 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 no conflict of interest.</p></sec><sec><title>Funding</title><p>Funding. The study had no sponsorship.</p></sec><sec><title>Received</title><p>Received: September 4, 2025 / Accepted: October 15, 2025 / Published: December 19, 2025</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>вегетативная нервная система</kwd><kwd>школьники-подростки</kwd><kwd>ген ApoE</kwd><kwd>ген SIRT1</kwd><kwd>тяжёлые металлы</kwd><kwd>биоэкспозиция</kwd></kwd-group><kwd-group xml:lang="en"><kwd>autonomic nervous system</kwd><kwd>adolescent schoolchildren</kwd><kwd>ApoE gene</kwd><kwd>SIRT1 gene</kwd><kwd>heavy metals</kwd><kwd>bioexposure</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">Zhang H., Wang J., Zhang K., Shi J., Gao Y., Zheng J., et al. Association between heavy metals exposure and persistent infections: the mediating role of immune function. Front. Public Health. 2024; 12: 1367644. https://doi.org/10.3389/fpubh.2024.1367644</mixed-citation><mixed-citation xml:lang="en">Zhang H., Wang J., Zhang K., Shi J., Gao Y., Zheng J., et al. Association between heavy metals exposure and persistent infections: the mediating role of immune function. Front. Public Health. 2024; 12: 1367644. https://doi.org/10.3389/fpubh.2024.1367644</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Akash M.S.H., Yaqoob A., Rehman K., Imran M., Assiri M.A., Al-Rashed F., et al. Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities. Front. Mol. Biosci. 2023; 10: 1218497. https://doi.org/10.3389/fmolb.2023.1218497</mixed-citation><mixed-citation xml:lang="en">Akash M.S.H., Yaqoob A., Rehman K., Imran M., Assiri M.A., Al-Rashed F., et al. Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities. Front. Mol. Biosci. 2023; 10: 1218497. https://doi.org/10.3389/fmolb.2023.1218497</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Чутко Л.С., Сурушкина С.Ю., Яковенко Е.А., Корнишина Т.Л. Вегето-сосудистая дистония у детей и подростков. Клинико-психофизиологические проявления и терапия (обзор). Практика педиатра. 2019; (3): 17–21. https://elibrary.ru/hfvwmg</mixed-citation><mixed-citation xml:lang="en">Chutko L.S., Surushkina S.Yu., Yakovenko E.A., Kornishina T.L. Vegetative dysfunction in children and adolescents. Clinical and psychophysiological manifestations and therapy (review). Praktika pediatra. 2019; (3): 17–21. https://elibrary.ru/hfvwmg (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Чутко Л.С., Корнишина Т.Л., Сурушкина С.Ю., Яковенко Е.А., Анисимова Т.И., Волов М.Б. Синдром вегетативной дисфункции у детей и подростков. Журнал неврологии и психиатрии им. С.С. Корсакова. 2018; 118(1): 43–9. https://doi.org/10.17116/jnevro20181181143-49 https://elibrary.ru/ypbucs</mixed-citation><mixed-citation xml:lang="en">Chutko L.S., Kornishina T.L., Surushkina S.Yu., Yakovenko E.A., Anisimova T.I., Volov M.B. Syndrome of autonomic dysfunction in children and adolescents. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2018; 118(1): 43–9. https://doi.org/10.17116/jnevro20181181143-49 https://elibrary.ru/ypbucs (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Sasaki N., Carpenter D.O. Associations between metal exposures and cognitive function in American older adults. Int. J. Environ. Res. Public Health. 2022; 19(4): 2327. https://doi.org/10.3390/ijerph19042327</mixed-citation><mixed-citation xml:lang="en">Sasaki N., Carpenter D.O. Associations between metal exposures and cognitive function in American older adults. Int. J. Environ. Res. Public Health. 2022; 19(4): 2327. https://doi.org/10.3390/ijerph19042327</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Cervantes Vázquez G.I., González Esquivel D.F., Ramírez Ortega D., Blanco Ayala T., Ramos Chávez L.A., López-López H.E., et al. Mechanisms associated with cognitive and behavioral impairment induced by arsenic exposure. Cells. 2023; 12: 2537. https://doi.org/10.3390/cells12212537</mixed-citation><mixed-citation xml:lang="en">Cervantes Vázquez G.I., González Esquivel D.F., Ramírez Ortega D., Blanco Ayala T., Ramos Chávez L.A., López-López H.E., et al. Mechanisms associated with cognitive and behavioral impairment induced by arsenic exposure. Cells. 2023; 12: 2537. https://doi.org/10.3390/cells12212537</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The effects of cadmium toxicity. Int. J. Environ. Res. Public Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782</mixed-citation><mixed-citation xml:lang="en">Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The effects of cadmium toxicity. Int. J. Environ. Res. Public Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Halabicky O.M., Pinto-Martin J.A, Compton P., Liu J. Early childhood lead exposure and adolescent heart rate variability: A longitudinal cohort study. Environ. Res. 2022; 205: 112551. https://doi.org/10.1016/j.envres.2021.112551</mixed-citation><mixed-citation xml:lang="en">Halabicky O.M., Pinto-Martin J.A, Compton P., Liu J. Early childhood lead exposure and adolescent heart rate variability: A longitudinal cohort study. Environ. Res. 2022; 205: 112551. https://doi.org/10.1016/j.envres.2021.112551</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Газенкампф К.А., Доморацкая Е.А., Дмитренко Д.В. Генетические предикторы развития вегетативной дисфункции. Доктор.Ру. 2023; 22(6): 54–9. https://doi.org/10.31550/1727-2378-2023-22-6-54-59 https://elibrary.ru/oqyyrw</mixed-citation><mixed-citation xml:lang="en">Gazenkampf K.A., Domoratskaya H.E., Dmitrenko D.V. Genetic predictors of the development of autonomic dysfunction. Doktor.Ru. 2023; 22(6): 54–9. https://doi.org/10.31550/1727-2378-2023-22-6-54-59 https://elibrary.ru/oqyyrw (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Пухальская А.Э., Кветной И.М., Линькова Н.С., Дятлова А.С., Гутоп Е.О., Козлов К.Л. и др. Сиртуины и старение. Успехи физиологических наук. 2022; 53(1): 16–27. https://doi.org/10.31857/S0301179821040056 https://elibrary.ru/kunlxb</mixed-citation><mixed-citation xml:lang="en">Pukhalskaia A.E., Kvetnoy I.M., Linkova N.S., Diatlova A.S., Gutop E.O., Kozlov K.L., et al. Sirtuins and aging. Uspekhi fiziologicheskikh nauk. 2022; 53(1): 16–27. https://doi.org/10.31857/S0301179821040056 https://elibrary.ru/kunlxb (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Fujita Y., Yamashita T. Sirtuins in neuroendocrine regulation and neurological diseases. Front. Neurosci. 2018; 12: 778. https://doi.org/10.3389/fnins.2018.00778</mixed-citation><mixed-citation xml:lang="en">Fujita Y., Yamashita T. Sirtuins in neuroendocrine regulation and neurological diseases. Front. Neurosci. 2018; 12: 778. https://doi.org/10.3389/fnins.2018.00778</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Yan J., Tang X., Zhou Z.Q., Zhang J., Zhao Y., Li S., et al. Sirtuins functions in central nervous system cells under neurological disorders. Front. Physiol. 2022; 13: 886087. https://doi.org/10.3389/fphys.2022.886087</mixed-citation><mixed-citation xml:lang="en">Yan J., Tang X., Zhou Z.Q., Zhang J., Zhao Y., Li S., et al. Sirtuins functions in central nervous system cells under neurological disorders. Front. Physiol. 2022; 13: 886087. https://doi.org/10.3389/fphys.2022.886087</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Manjula R., Anuja K., Alcain F.J. SIRT1 and SIRT2 activity control in neurodegenerative diseases. Front. Pharmacol. 2021; 11: 585821. https://doi.org/10.3389/fphar.2020.585821</mixed-citation><mixed-citation xml:lang="en">Manjula R., Anuja K., Alcain F.J. SIRT1 and SIRT2 activity control in neurodegenerative diseases. Front. Pharmacol. 2021; 11: 585821. https://doi.org/10.3389/fphar.2020.585821</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ministrini S., Puspitasari Y.M., Beer G., Liberale L., Montecucco F., Camici G.G. Sirtuin 1 in endothelial dysfunction and cardiovascular aging. Front. Physiol. 2021; 12: 733696. https://doi.org/10.3389/fphys.2021.733696</mixed-citation><mixed-citation xml:lang="en">Ministrini S., Puspitasari Y.M., Beer G., Liberale L., Montecucco F., Camici G.G. Sirtuin 1 in endothelial dysfunction and cardiovascular aging. Front. Physiol. 2021; 12: 733696. https://doi.org/10.3389/fphys.2021.733696</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Rao W., Zhang Y., Li K., Zhang X.Y. Association between cognitive impairment and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia. Aging (Albany NY). 2021; 13(12): 16353–66. https://doi.org/10.18632/aging.203161</mixed-citation><mixed-citation xml:lang="en">Rao W., Zhang Y., Li K., Zhang X.Y. Association between cognitive impairment and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia. Aging (Albany NY). 2021; 13(12): 16353–66. https://doi.org/10.18632/aging.203161</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Доклад «О состоянии и об охране окружающей среды Пермского края в 2024 году». Пермь; 2024.</mixed-citation><mixed-citation xml:lang="en">Report «On the state and environmental protection of the Perm Region in 2024». Perm; 2024. (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Sadhukhan D., Mishra S., Mukherjee P., Biswas А., Hui S.P., Banerjee T.K., et al. Evaluation of Apolipoprotein e4 allele as susceptible factor for neurodegenerative diseases among Eastern Indians. Austin Alzheimers J. Parkinsons Dis. 2023; 6(2): 1040. https://doi.org/10.1101/2023.06.21.23291697</mixed-citation><mixed-citation xml:lang="en">Sadhukhan D., Mishra S., Mukherjee P., Biswas А., Hui S.P., Banerjee T.K., et al. Evaluation of Apolipoprotein e4 allele as susceptible factor for neurodegenerative diseases among Eastern Indians. Austin Alzheimers J. Parkinsons Dis. 2023; 6(2): 1040. https://doi.org/10.1101/2023.06.21.23291697</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Altaher A.M., Foad A.M., Youssef W., Ahmed A.E. Association of SIRT1 (rs7069102) Gene polymorphism with premature myocardial infarction in young Egyptian patients. Egypt. J. Med. Hum. Genet. 2024; 25: 121. https://doi.org/10.1186/s43042-024-00589-0</mixed-citation><mixed-citation xml:lang="en">Altaher A.M., Foad A.M., Youssef W., Ahmed A.E. Association of SIRT1 (rs7069102) Gene polymorphism with premature myocardial infarction in young Egyptian patients. Egypt. J. Med. Hum. Genet. 2024; 25: 121. https://doi.org/10.1186/s43042-024-00589-0</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Yang Y., Li Y., Li R., Wang Z. Research progress on arsenic, arsenic-containing medicinal materials, and arsenic-containing preparations: clinical application, pharmacological effects, and toxicity. Front. Pharmacol. 2024; 15: 1338725. https://doi.org/10.3389/fphar.2024.1338725</mixed-citation><mixed-citation xml:lang="en">Yang Y., Li Y., Li R., Wang Z. Research progress on arsenic, arsenic-containing medicinal materials, and arsenic-containing preparations: clinical application, pharmacological effects, and toxicity. Front. Pharmacol. 2024; 15: 1338725. https://doi.org/10.3389/fphar.2024.1338725</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Thakur M., Rachamalla M., Niyogi S., Datusalia A.K., Flora S.J.S. Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions. Int. J. Mol. Sci. 2021; 10077. https://doi.org/10.3390/ijms221810077</mixed-citation><mixed-citation xml:lang="en">Thakur M., Rachamalla M., Niyogi S., Datusalia A.K., Flora S.J.S. Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions. Int. J. Mol. Sci. 2021; 10077. https://doi.org/10.3390/ijms221810077</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Batool Z., Agha F., Tabassum S., Batool T.S., Siddiqui R.A., Haider S. Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts. Acta Neurobiol. Exp. (Wars). 2019; 79(2): 169–83.</mixed-citation><mixed-citation xml:lang="en">Batool Z., Agha F., Tabassum S., Batool T.S., Siddiqui R.A., Haider S. Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts. Acta Neurobiol. Exp. (Wars). 2019; 79(2): 169–83.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Рябова Ю.В., Шабардина Л.В., Кескевич А.А., Минигалиева И.А., Сутункова М.П., Бутакова И.В. и др. Нейротоксические эффекты сочетанного действия хлорида кадмия и физической нагрузки и протекторное действие биопрофилактических средств. Гигиена и санитария. 2024; 103(2): 165–71. https://doi.org/10.47470/0016-9900-2024-103-2-165-171 https://elibrary.ru/uapwut</mixed-citation><mixed-citation xml:lang="en">Ryabova Yu.V., Shabardina L.V., Keskevich A.A., Minigalieva I.A., Sutunkova M.P., Butakova I.V., et al. Neurotoxic effects of cadmium chloride exposure combined with physical activity and protective effect of bioprophylactic agents. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2024; 103(2): 165–71. https://doi.org/10.47470/0016-9900-2024-103-2-165-171 https://elibrary.ru/uapwut (in Russian)</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Ramírez Ortega D., González Esquivel D.F., Blanco Ayala T., Pineda B., Gómez Manzo S., Marcial Quino J., et al. Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity. Toxics. 2021; 9(2): 23. https://doi.org/10.3390/toxics9020023</mixed-citation><mixed-citation xml:lang="en">Ramírez Ortega D., González Esquivel D.F., Blanco Ayala T., Pineda B., Gómez Manzo S., Marcial Quino J., et al. Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity. Toxics. 2021; 9(2): 23. https://doi.org/10.3390/toxics9020023</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Krajewski K. Heavy metals, noradrenaline/adrenaline ratio, and microbiome-associated hormone precursor metabolites: biomarkers for social behaviour, ADHD symptoms, and executive function in children. Sci. Rep. 2025; 15(1): 19006. https://doi.org/10.1038/s41598-025-00680-5</mixed-citation><mixed-citation xml:lang="en">Krajewski K. Heavy metals, noradrenaline/adrenaline ratio, and microbiome-associated hormone precursor metabolites: biomarkers for social behaviour, ADHD symptoms, and executive function in children. Sci. Rep. 2025; 15(1): 19006. https://doi.org/10.1038/s41598-025-00680-5</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Dobrakowski M., Kasperczyk A., Czuba Z.P., Machoń-Grecka A., Szlacheta Z., Kasperczyk S. The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans. Hum. Exp. Toxicol. 2017; 36(6): 587–93. https://doi.org/10.1177/0960327116658106</mixed-citation><mixed-citation xml:lang="en">Dobrakowski M., Kasperczyk A., Czuba Z.P., Machoń-Grecka A., Szlacheta Z., Kasperczyk S. The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans. Hum. Exp. Toxicol. 2017; 36(6): 587–93. https://doi.org/10.1177/0960327116658106</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Nguyen J., Patel A., Gensburg A., Bokhari R., Lamar P, Edwards J. Diabetogenic and obesogenic effects of cadmium in Db/Db mice and rats at a clinically relevant level of exposure. Toxics. 2022; 10(3): 107. https://doi.org/10.3390/toxics10030107</mixed-citation><mixed-citation xml:lang="en">Nguyen J., Patel A., Gensburg A., Bokhari R., Lamar P, Edwards J. Diabetogenic and obesogenic effects of cadmium in Db/Db mice and rats at a clinically relevant level of exposure. Toxics. 2022; 10(3): 107. https://doi.org/10.3390/toxics10030107</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Montalbano A.M., Albano G.D., Bonanno A., Riccobono L., Di Sano C., Ferraro M., et al. Autocrine acetylcholine, Induced by IL-17A via NFκB and ERK1/2 pathway activation, promotes MUC5AC and IL-8 synthesis in bronchial epithelial cells. Mediators Inflamm. 2016; 2016: 9063842. https://doi.org/10.1155/2016/9063842</mixed-citation><mixed-citation xml:lang="en">Montalbano A.M., Albano G.D., Bonanno A., Riccobono L., Di Sano C., Ferraro M., et al. Autocrine acetylcholine, Induced by IL-17A via NFκB and ERK1/2 pathway activation, promotes MUC5AC and IL-8 synthesis in bronchial epithelial cells. Mediators Inflamm. 2016; 2016: 9063842. https://doi.org/10.1155/2016/9063842</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang L., Tu R., Wang Y., Hu Y., Li X., Cheng X., et al. Early-life exposure to lead induces cognitive impairment in elder mice targeting SIRT phosphorylation and oxidative alterations. Front. Physiol. 2017; 8: 446. https://doi.org/10.3389/fphys.2017.00446</mixed-citation><mixed-citation xml:lang="en">Zhang L., Tu R., Wang Y., Hu Y., Li X., Cheng X., et al. Early-life exposure to lead induces cognitive impairment in elder mice targeting SIRT phosphorylation and oxidative alterations. Front. Physiol. 2017; 8: 446. https://doi.org/10.3389/fphys.2017.00446</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>
