toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2024-32-2-63-71rknhsmtoxreview-816Research ArticleОБЗОРЫREVIEWSПерспективы применения генистеина для лечения отравлений химическими веществами гепатотоксического действия (обзор литературы)Prospects for the use of genistein for the treatment of poisoning with hepatotoxic chemicals (literature review)https://orcid.org/0009-0006-2202-7919ЕрлинГлеб ВладимировичErlinGleb V.

Аспирант 1-го курса направления токсикология кафедры фармацевтической химии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» МЗ РФ, г. Санкт-Петербург

e-mail: gleb.erlin@spcpu.ru 

1st year postgraduate student in toxicology, Department of Pharmaceutical Chemistry, Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg, Russian Federation

e-mail: gleb.erlin@spcpu.ru

gleb.erlin@spcpu.ruhttps://orcid.org/0000-0001-6737-1023СтреловаОльга ЮрьевнаStrelovaOlga Yu.

Доктор фармацевтических наук, профессор, заведующая кафедрой фармацевтической химии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» МЗ РФ, г. Санкт-Петербург

e-mail: olga.strelova@pharminnotech.com

Doctor of Pharmaceutical Sciences, Associate Professor, Head of the Department of Pharmaceutical Chemistry, Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg, Russian Federation

e-mail: olga.strelova@pharminnotech.com

olga.strelova@pharminnotech.comhttps://orcid.org/0000-0002-9381-194XГребенюкАлександр НиколаевичGrebenyukAleksandr N.

Доктор медицинских наук, профессор, профессор кафедры фармацевтической химии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» МЗ РФ, г. Санкт-Петербург; профессор кафедры мобилизационной подготовки здравоохранения и медицины катастроф ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И.П. Павлова» МЗ РФ, г. Санкт-Петербург

e-mail: grebenyuk_an@mail.ru

Doctor of Medical Sciences, Professor of the Department of Pharmaceutical Chemistry, Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg. Professor of the Department of Mobilization Training of Healthcare and Disaster Medicine of the Federal State Budgetary Educational Institution of Higher Education “First Pavlov State Medical University of St. Petersburg" Ministry of Health of the Russian Federation, St. Petersburg, Russian Federation

e-mail: grebenyuk_an@mail.ru

grebenyuk_an@mail.ruФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской ФедерацииРоссияSaint Petersburg State Chemical and Pharmaceutical UniversityRussian FederationФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияSaint Petersburg State Chemical and Pharmaceutical University; Pavlov First Saint Petersburg State Medical University (Pavlov UniversityRussian Federation2024270420243226371Copyright © Ерлин Г.В., Стрелова О.Ю., Гребенюк А.Н., 20242024Ерлин Г.В., Стрелова О.Ю., Гребенюк А.Н.Erlin G.V., Strelova O.Y., Grebenyuk A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/816Введение

Введение. Поиск новых высокоэффективных лекарственных средств с широким спектром фармакологического действия и низкой токсичностью является одним из приоритетных направлений развития современной фармации и медицины. Актуальной остается разработка лекарственных средств, предназначенных для лечения отравлений химическими веществами гепатотоксического действия. Большой интерес в этом плане представляют вещества растительного происхождения, в частности генистеин.

Материал и методы

Материал и методы. Материалом для анализа послужили источники литературы, реферированные в библиографических базах PubMed, Scopus, РИНЦ.

Результаты

Результаты. В статье обсуждаются результаты отечественных и зарубежных исследований, посвященных изучению биологического действия генистеина. Описывается его структура, токсичность и механизмы фармакологического действия. Рассматриваются результаты исследований, подтверждающие эффективность генистеина в защите печени, а также в снижении токсического воздействия на этот орган при отравлениях. Выделяется раздел, в котором рассматривается возможность применения генистеина в различных медицинских областях и его потенциал для профилактики и лечения патологий, вызванных гепатотоксикантами.

Ограничения исследования

Ограничения исследования. Обзор подготовлен на основе изучения 44 источников литературы, опубликованных за период с 1998 по 2023 год, что представляет собой достаточно референтную выборку.

Заключение

Заключение. Генистеин, имеющий выраженную антиоксидантную активность, потенциально может быть использован для лечения отравлений химическими веществами, в механизме токсического действия которых важную роль играет оксидативный стресс, прежде всего гепатотоксикантов.

Участие авторов

Участие авторов:Ерлин Г.В. — сбор материала в библиографических базах, обработка и анализ материала, написание текста;Стрелова О.Ю. — анализ материала, обработка и редактирование текста;Гребенюк А.Н. — концепция и дизайн исследования; анализ материала, обработка и редактирование текста.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Поступила в редакцию

Поступила в редакцию: 27.12.2023 / Принята в печать: 10.03.2024 / Опубликована: 27.04.2024

Introduction

Introduction. The search for new highly effective medicines with a wide range of pharmacological effects and low toxicity is one of the priorities of the development of modern pharmacy and medicine. The development of medicines intended for the treatment of poisoning by chemical substances of hepatotoxic action remains actual. Substances of plant origin, in particular genistein, are of great interest in this regard.

Material and methods

Material and methods. The material for the analysis was the sources of literature, abstracting in the bibliographic databases of PubMed, Scopus, and RSCI.

Results

Results. The article discusses the results of domestic and foreign studies devoted to the study of the biological effect of genistein. Its structure, toxicity and mechanisms of action are described. The results of studies confirming the effectiveness of genistein in protecting the liver, as well as in reducing the toxic effects on this organ in case of poisoning, are considered. A section is highlighted that examines the possibility of using genistein in various medical fields and its potential for the prevention and treatment of pathologies caused by hepatotoxicants.

Limitations

Limitations. The review was prepared based on a study of 44 literature sources published over the period from 1998 to 2023, which represents a fairly representative sample.

Conclusion

Conclusion. Genistein, which has a pronounced antioxidant activity, can potentially be used to treat poisoning with chemicals, in the mechanism of toxic action of which oxidative stress plays an important role, primarily hepatotoxicants.

Аuthors сontribution

Аuthors сontribution:Erlin G.V. — collection of material in bibliographic databases, material analysis, writing the text of the article;Strelova O.Yu. — material analysis, text processing and editing;Grebenyuk A.N. — the concept and design of the study, material analysis, text processing and editing.All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interests

Conflict of interests. The authors declare no conflict of interest.

Funding

Funding. The study had no sponsorship.

Received

Received: December 27, 2023 / Accepted: March 10, 2024 / Published: April 27, 2024

генистеинфлавоноидантиоксидантгепатотоксикантотравлениелечениеобзорgenisteinflavonoidantioxidanthepatotoxicantpoisoningtreatmentreviewReferencesГребенюк А.Н., Бояринцев В.В., Сидоров Д.А. Современные подходы к организации и проведению мероприятий экстренной медицинской помощи при массовых острых отравлениях. Кремлевская медицина. Клинический вестник. 2015; 2: 8–16.Grebenyuk A.N., Boyarincev V.V., Sidorov D.A. Modern approaches to the organization and conduct of emergency medical care in case of mass acute poisoning. Kremlevskaya meditsina. Klinicheskiy vestnik. 2015; 2: 8–16. (in Russian)Tuli H.S., Tuorkey M.J., Thakral F., Sak K., Kumar M., Sharma A.K., et al. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances. Front. Pharmacol. 2019; 10: 1336. https://doi.org/10.3389/fphar.2019.01336Tuli H.S., Tuorkey M.J., Thakral F., Sak K., Kumar M., Sharma A.K., et al. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances. Front. Pharmacol. 2019; 10: 1336. https://doi.org/10.3389/fphar.2019.01336Han R.-M., Tian Y.-X., Liu Y., Chen Ch.-H., Ai X.-Ch., Zhang J.-P. et al. Comparison of Flavonoids and Isoflavonoids as Antioxidants. J. Agric. Food. Chem. 2009; 57: 3780–5. https://doi.org/10.1021/jf803850pHan R.-M., Tian Y.-X., Liu Y., Chen Ch.-H., Ai X.-Ch., Zhang J.-P. et al. Comparison of Flavonoids and Isoflavonoids as Antioxidants. J. Agric. Food. Chem. 2009; 57: 3780–5. https://doi.org/10.1021/jf803850pТарумов Р.А., Башарин В.А., Гребенюк А.Н. Противолучевые свойства современных антиоксидантов. Биомедицинский журнал Medline.Ru. 2012; 13: 682–700.Tarumov R.A., Basharin V.A., Grebenyuk A.N. Anti-radiation properties of modern antioxidants. Biomeditsinskiy zhurnal Medline.Ru. 2012; 13: 682–700. (In Russian)Тарумов Р.А., Гребенюк А.Н., Башарин В.А., Ковтун В.Ю. Биологические свойства фитоэстрогена генистеина (обзор литературы). Медицина экстремальных ситуаций. 2014; 2(48): 55–68.Tarumov R.A., Grebenyuk A.N., Basharin V.A., Kovtun V.YU. Biological properties of the phytoestrogen genistein. Meditsina ekstremal’nykh situatsiy. 2014; 2: 55–68. (In Russian)Жигалина А.А., Дударев В.Г., Тихонова В.В., Стрелова О.Ю. Разработка синтеза генистеина для использования в качестве стандартного образца. Разработка и регистрация лекарственных средств. 2021; 10(4): 20–31. https://doi.org/10.33380/2305-2066-2021-10-4(1)-20-31Zhigalina A.A., Dudarev V.G., Tikhonova V.V., Strelova O.Yu. Development of genistein synthesis for use as a certified reference material. Razrabotka i registratsiya lekarstvennykh sredstv. 2021; 10(4–1): 20–31. https://doi.org/10.33380/2305-2066-2021-10-4(1)-20-31 (In Russian)McClain R.M., Wolz E., Davidovich A., Pfannkuch F., Edwards J.A., Bausch J. Acute, subchronic and chronic safety studies with genistein in rats. Food Chem. Toxicol. 2006; 44(1): 56–80. https://doi.org/10.1016/j.fct.2005.05.021McClain R.M., Wolz E., Davidovich A., Pfannkuch F., Edwards J.A., Bausch J. Acute, subchronic and chronic safety studies with genistein in rats. Food Chem. Toxicol. 2006; 44(1): 56–80. https://doi.org/10.1016/j.fct.2005.05.021Гребенюк А.Н., Башарин В.А., Тарумов Р.А., Назаров В.Б., Ковтун В.Ю., Чику-нов И.Е. Экспериментальное исследование острой токсичности генистеина в опытах на мелких лабораторных животных. Токсикологический вестник. 2012; 6(116): 25–9.Grebenyuk A.N., Basharin V.A., Tarumov R.A., Nazarov V.B., Kovtun V.Yu., Chikunov I.E. Experimental study of acute toxicity of genistein in experiments on small laboratory animals. Toksikologicheskiy vestnik. 2012; 6(116): 25–29. (In Russian)Chang Y., Choue R. Plasmapharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women. Nutr. Res. Pract. 2013; 7(5): 393–9. https://doi.org/10.4162/nrp.2013.7.5.393Chang Y., Choue R. Plasmapharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women. Nutr. Res. Pract. 2013; 7(5): 393–9. https://doi.org/10.4162/nrp.2013.7.5.393Busby M.G., Jeffcoat A.R., Bloedon L.T., Koch M.A., Black T., Dix K.J. et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am. J. Clin. Nutr. 2002; 75: 126–36. https://doi.org/10.1093/ajcn/75.1.126Busby M.G., Jeffcoat A.R., Bloedon L.T., Koch M.A., Black T., Dix K.J. et al. Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men. Am. J. Clin. Nutr. 2002; 75: 126–36. https://doi.org/10.1093/ajcn/75.1.126Sepehr E., Cooke G.M., Robertson P., Gilani G.S. Effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged male rats. Mol. Nutr. Food Res. 2009; 1: 16–26. https://doi.org/10.1002/mnfr.200800170Sepehr E., Cooke G.M., Robertson P., Gilani G.S. Effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged male rats. Mol. Nutr. Food Res. 2009; 1: 16–26. https://doi.org/10.1002/mnfr.200800170Mazurek A.P., Kozerski L., Sadlej J., Kawecki R., Bednarek E., Sitkowski J. et al. Genistein complexes with amines structure and properties. J. Chem. Soc, Perkin Trans. 1998; 2: 1223–30. https://doi.org/10.1039/A708956BMazurek A.P., Kozerski L., Sadlej J., Kawecki R., Bednarek E., Sitkowski J. et al. Genistein complexes with amines structure and properties. J. Chem. Soc, Perkin Trans. 1998; 2: 1223–30. https://doi.org/10.1039/A708956BSanjeev B., Yiwei L., Zhiwei W., Fazlul H.S. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008; 269(2): 226–42. https://doi.org/10.1016/j.canlet.2008.03.052Sanjeev B., Yiwei L., Zhiwei W., Fazlul H.S. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008; 269(2): 226–42. https://doi.org/10.1016/j.canlet.2008.03.052Li Q.S., Li C.Y., Li Z.L., Zhu H.L. Genistein and Its Synthetic Analogs as Anticancer Agents. Anticancer Agents Med. Chem. 2012; 12: 271–81. https://doi.org/10.2174/187152012800228788Li Q.S., Li C.Y., Li Z.L., Zhu H.L. Genistein and Its Synthetic Analogs as Anticancer Agents. Anticancer Agents Med. Chem. 2012; 12: 271–81. https://doi.org/10.2174/187152012800228788Tiulea C., Peev C., Brezovan D., Dehelean C., Motoc A. A comparison regarding antiproliferative action between soy total extract and genistein. Rom. J. Morphol. Embryol. 2011; 52: 1065–9.Tiulea C., Peev C., Brezovan D., Dehelean C., Motoc A. A comparison regarding antiproliferative action between soy total extract and genistein. Rom. J. Morphol. Embryol. 2011; 52: 1065–9.Patisaul H.B., Jefferson W. The pros and cons of phytoestrogens. Front. Neuroendocrinol. 2010; 31(4): 1–45. https://doi.org/10.1016/j.yfrne.2010.03.003Patisaul H.B., Jefferson W. The pros and cons of phytoestrogens. Front. Neuroendocrinol. 2010; 31(4): 1–45. https://doi.org/10.1016/j.yfrne.2010.03.003Huang C., Qiao X., Dong B. Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats. Br. J. Nutr. 2011; 106: 105–13. https://doi.org/10.1017/S0007114510005799Huang C., Qiao X., Dong B. Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats. Br. J. Nutr. 2011; 106: 105–13. https://doi.org/10.1017/S0007114510005799Pinzani M. Pathophysiology of non-alcoholic steatohepatitis and basis for treatment. Dig. Dis. 2011; 29: 243–8. https://doi.org/10.1159/000323928Pinzani M. Pathophysiology of non-alcoholic steatohepatitis and basis for treatment. Dig. Dis. 2011; 29: 243–8. https://doi.org/10.1159/000323928Ji G., Yang Q., Hao J., Guo L., Chen X., Hu J. et al. Antiinflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanism. Int. Immunopharmacol. 2011; 11: 762–8. https://doi.org/10.1016/j.intimp.2011.01.036Ji G., Yang Q., Hao J., Guo L., Chen X., Hu J. et al. Antiinflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanism. Int. Immunopharmacol. 2011; 11: 762–8. https://doi.org/10.1016/j.intimp.2011.01.036Szkudelska K., Nogowski L., Szkudelski T. Resveratrol and genistein as adenosine triphosphate-depleting agents in fat cells. Metabolism. 2011; 60: 720–9. https://doi.org/10.1016/j.metabol.2010.07.006Szkudelska K., Nogowski L., Szkudelski T. Resveratrol and genistein as adenosine triphosphate-depleting agents in fat cells. Metabolism. 2011; 60: 720–9. https://doi.org/10.1016/j.metabol.2010.07.006Turan B., Tuncay E., Vassort G. Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies. J. Bioenerg. Biomembr. 2012; 44: 281–96. https://doi.org/10.1007/s10863-012-9429-0Turan B., Tuncay E., Vassort G. Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies. J. Bioenerg. Biomembr. 2012; 44: 281–96. https://doi.org/10.1007/s10863-012-9429-0Kim M.H., Park J.S., Seo M.S., Jung J.W., Lee Y.S., Kang K.S. Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/beta-catenin signalling or lipolysis. Cell Prolif. 2010; 43: 594–605. https://doi.org/10.1111/j.1365-2184.2010.00709.xKim M.H., Park J.S., Seo M.S., Jung J.W., Lee Y.S., Kang K.S. Genistein and daidzein repress adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via Wnt/beta-catenin signalling or lipolysis. Cell Prolif. 2010; 43: 594–605. https://doi.org/10.1111/j.1365-2184.2010.00709.xWahajuddin, Taneja I., Arora S., Raju K.S., Siddiqui N. Disposition of Pharmacologically Active Dietary Isoflavones in Biological Systems. Curr. Drug Metab. 2010; 14: 369–80. https://doi.org/10.2174/1389200211314040002Wahajuddin, Taneja I., Arora S., Raju K.S., Siddiqui N. Disposition of Pharmacologically Active Dietary Isoflavones in Biological Systems. Curr. Drug Metab. 2010; 14: 369–80. https://doi.org/10.2174/1389200211314040002Sacks F.M., Lichtenstein A., Van Horn L., Harris W., Kris-Etherton P., Winston M. Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation. 2006; 113(7): 1034–44. https://doi.org/10.1161/CIRCULATIONAHA.106.171052Sacks F.M., Lichtenstein A., Van Horn L., Harris W., Kris-Etherton P., Winston M. Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation. 2006; 113(7): 1034–44. https://doi.org/10.1161/CIRCULATIONAHA.106.171052Si H., Liu D. Phytochemical genistein in the regulation of vascular function: new insights. Curr. Med. Chem. 2007; 14(24): 2581–9. https//doi.org/10.2174/092986707782023325Si H., Liu D. Phytochemical genistein in the regulation of vascular function: new insights. Curr. Med. Chem. 2007; 14(24): 2581–9. https//doi.org/10.2174/092986707782023325Li H.J., Wu N.L., Lee G.A., Hung C.F. The Therapeutic Potential and Molecular Mechanism of Isoflavone Extract against Psoriasis. Sci. Rep. 2018; 8: 6335. https://www.nature.com/articles/s41598-018-24726-zLi H.J., Wu N.L., Lee G.A., Hung C.F. The Therapeutic Potential and Molecular Mechanism of Isoflavone Extract against Psoriasis. Sci. Rep. 2018; 8: 6335. https://www.nature.com/articles/s41598-018-24726-zКузнецова И.В. Эффективность и безопасность генистеина в лечении вазомоторных симптомов у женщин в постменопаузе (обзор исследований). Гинекология. 2013; 15(3): 4–9.Kuznecova I.V. Efficacy and safety of genistein in the treatment of vasomotor symptoms in postmenopausal women (research review). Ginekologiya. 2013; 15(3): 4–9. (In Russian)Zhang Y., Wang G.-J., Song T.T., Murphy P.A., Hendrich S. Urinary Disposition of the Soybean Isofavones Daidzein, Genistein and Glycitein Differs among Humans with Moderate Fecal Isoflavone Degradation Activity. J. Nutr. 1999; 129: 957–62. https://doi.org/10.1093/jn/129.5.957Zhang Y., Wang G.-J., Song T.T., Murphy P.A., Hendrich S. Urinary Disposition of the Soybean Isofavones Daidzein, Genistein and Glycitein Differs among Humans with Moderate Fecal Isoflavone Degradation Activity. J. Nutr. 1999; 129: 957–62. https://doi.org/10.1093/jn/129.5.957Miadoková E. Isoflavonoids – an overview of their biological activities and potential health benefits. Interdiscip Toxicol. 2009; 2 (4): 211–8. https://doi.org/10.2478/v10102-009-0021-3Miadoková E. Isoflavonoids – an overview of their biological activities and potential health benefits. Interdiscip Toxicol. 2009; 2 (4): 211–8. https://doi.org/10.2478/v10102-009-0021-3Mawarni B., Sri O., Fitra F. Antioxidant Activities of Genistein: A Review. Int. J. Pharm. Sci. Med. 2020; 5: 19–23. https://doi.org/10.47760/ijpsm.2020.v05i10.001Mawarni B., Sri O., Fitra F. Antioxidant Activities of Genistein: A Review. Int. J. Pharm. Sci. Med. 2020; 5: 19–23. https://doi.org/10.47760/ijpsm.2020.v05i10.001Hwang T.C., Koeppe R.E. 2nd, Andersen O.S. Genistein can modulate channel function by a phosphorylation-independent mechanism: importance of hydrophobic mismatch and bilayer mechanics. Biochemistry. 2003; 42(46): 13646–58. https://doi.org/10.1021/bi034887yHwang T.C., Koeppe R.E. 2nd, Andersen O.S. Genistein can modulate channel function by a phosphorylation-independent mechanism: importance of hydrophobic mismatch and bilayer mechanics. Biochemistry. 2003; 42(46): 13646–58. https://doi.org/10.1021/bi034887yГребенюк А.Н., Башарин В.А., Тарумов Р.А., Арутюнян А.В., Прокопенко В.М., Ковтун В.Ю. Оценка антиоксидантных свойств отечественного синтетического генистеина на моделях in vitro и in vivo. Вестник Российской Военно-медицинской академии. 2013; 2: 83–7.Grebenyuk A.N., Basharin V.A., Tarumov R.A., Arutyunyan A.V., Prokopenko V.M., Kovtun V.Yu. Evaluation of antioxidant properties of domestic synthetic genistein on in vitro and in vivo models. Vestnik Rossiyskoy Voenno-meditsinskoy akademii. 2013; 2: 83–7. (In Russian).Ding W., Liu Y. Genistein attenuates genioglossus muscle fatigue under chronic intermittent hypoxia by down-regulation of oxidative stress level and up-regulation of antioxidant enzyme activity through ERK1/2 signaling pathway. Oral Dis. 2011; 17: 677–84. https://doi.org/10.1111/j.1601-0825.2011.01822.xDing W., Liu Y. Genistein attenuates genioglossus muscle fatigue under chronic intermittent hypoxia by down-regulation of oxidative stress level and up-regulation of antioxidant enzyme activity through ERK1/2 signaling pathway. Oral Dis. 2011; 17: 677–84. https://doi.org/10.1111/j.1601-0825.2011.01822.xHsieh H.M., Wu W.M., Hu M.L. Genistein attenuates D-galactoseinduced oxidative damage through decreased reactive oxygen species and NFkappaB binding activity in neuronal PC12 cells. Life Sci. 2010; 88: 82–8. https://doi.org/10.1016/j.lfs.2010.10.021Hsieh H.M., Wu W.M., Hu M.L. Genistein attenuates D-galactoseinduced oxidative damage through decreased reactive oxygen species and NFkappaB binding activity in neuronal PC12 cells. Life Sci. 2010; 88: 82–8. https://doi.org/10.1016/j.lfs.2010.10.021Xi Y.D., Yu H.L., Ma W.W., Ding B.J., Ding J., Yuan L.H. et al. Genistein inhibits mitochondrial-targeted oxidative damage induced by beta-amyloid peptide 25–35 in PC12 cells. J. Bioenerg. Biomembr. 2011; 43(4): 399–407. https://doi.org/10.1007/s10863-011-9362-7Xi Y.D., Yu H.L., Ma W.W., Ding B.J., Ding J., Yuan L.H. et al. Genistein inhibits mitochondrial-targeted oxidative damage induced by beta-amyloid peptide 25–35 in PC12 cells. J. Bioenerg. Biomembr. 2011; 43(4): 399–407. https://doi.org/10.1007/s10863-011-9362-7Гребенюк А.Н., Тарумов Р.А., Башарин В.А., Ковтун В.Ю. Экспериментальная оценка радиозащитной эффективности синтетического генистеина по показателям системы глутатиона и перекисного окисления липидов в эритроцитах периферической крови облученных крыс. Радиационная биология. Радиоэкология. 2015; 55(5): 501–6.Grebenyuk A.N., Basharin V.A., Tarumov R.A., Kovtun V.YU., Pastushenkov V.L., Kovtun V.Yu. Experimental evaluation of the radioprotective effectiveness of synthetic genistein by indicators of the glutathione system and lipid peroxidation in peripheral blood erythrocytes of irradiated rats. Radiatsionnaya biologiya. Radioekologiya. 2015; 55(5): 501–6. (In Russian)Zhou Y., Mi M.T. Genistein stimulates hematopoiesis and increases survival in irradiated mice. J. Radiat. Res. 2005; 46(4): 425–33. https://doi.org/10.1269/jrr.46.425Zhou Y., Mi M.T. Genistein stimulates hematopoiesis and increases survival in irradiated mice. J. Radiat. Res. 2005; 46(4): 425–33. https://doi.org/10.1269/jrr.46.425Grace M.B., Blakely W.F., Landauer M.R. Genistein induced alterations of radiation-responsive gene expression. Radiat. Meas. 2007; 42(6–7): 1152–7.Grace M.B., Blakely W.F., Landauer M.R. Genistein induced alterations of radiation-responsive gene expression. Radiat. Meas. 2007; 42(6–7): 1152–7.Гребенюк А.Н., Башарин В.А., Тарумов Р.А., Пастушенков В.Л., Ковтун В.Ю. Экспериментальная оценка влияния синтетического генистеина на гематологические показатели и цитокиновый статус облученных крыс. Радиационная биология. Радиоэкология. 2015; 55 (2): 160–8.Grebenyuk A.N., Tarumov R.A., Basharin V.A. Experimental evaluation of the effect of synthetic genistein on hematological parameters and cytokine status of irradiated rats. Radiatsionnaya biologiya. Radioekologiya. 2015; 55(2): 160–8. (In Russian)Меснянкина О.А., Наумов В.З., Дегтярев О.В., Дуйко В.В. Свободнорадикальные процессы в патологии печени у лиц пожилого возраста. Астраханский медицинский журнал. 2011; 3: 39–43.Mesnyankina O.A., Naumov V.Z., Degtyarev O.V., Duyko V.V. Free radical processes in liver pathology in the elderly. Astrakhanskiy meditsinskiy zhurnal. 2011; 3: 39–43. (In Russian)Semeniuk M., Ceré L.I., Ciriaci N., Bucci-Muñoz M., Quiroga A.D., Luquita M.G. et al. Protective effect of genistein pre-treatment on paraquat hepatotoxicity in rats. Toxicol. Appl. Pharmacol. 2021; 426: 115636. https://doi.org/10.1016/j.taap.2021.115636Semeniuk M., Ceré L.I., Ciriaci N., Bucci-Muñoz M., Quiroga A.D., Luquita M.G. et al. Protective effect of genistein pre-treatment on paraquat hepatotoxicity in rats. Toxicol. Appl. Pharmacol. 2021; 426: 115636. https://doi.org/10.1016/j.taap.2021.115636Wang L., Li A., Liu Y., Zhan S., Zhong L., Du Y. et al. Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling. Biochem. Biophys. Res. Commun. 2020; 527(1): 90–7. https://doi.org/10.1016/j.bbrc.2020.04.100Wang L., Li A., Liu Y., Zhan S., Zhong L., Du Y. et al. Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling. Biochem. Biophys. Res. Commun. 2020; 527(1): 90–7. https://doi.org/10.1016/j.bbrc.2020.04.100Huang Q., Huang R., Zhang S., Lin J., Wei L., He M. et al. Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats. Toxicol. Lett. 2013; 217: 102–10. https://doi.org/10.1016/j.toxlet.2012.12.014Huang Q., Huang R., Zhang S., Lin J., Wei L., He M. et al. Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats. Toxicol. Lett. 2013; 217: 102–10. https://doi.org/10.1016/j.toxlet.2012.12.014Ayala-Calvillo E., Rodríguez-Fragoso L., Álvarez-Ayala E., Leija-Salas A. EGF‑receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage. J. Mol. Histol. 2023; 54: 231–44. https://doi.org/10.1007/s10735-023-10127-8Ayala-Calvillo E., Rodríguez-Fragoso L., Álvarez-Ayala E., Leija-Salas A. EGF‑receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage. J. Mol. Histol. 2023; 54: 231–44. https://doi.org/10.1007/s10735-023-10127-8

The authors declare that there are no conflicts of interest present.