medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2023-102-7-700-705keyvlzmedlit-3274Research ArticleМЕДИЦИНА ТРУДАOCCUPATIONAL HEALTHПатогенез морфологических изменений органов и тканей при хронической фтористой интоксикации (обзор литературы)Pathogenesis of morphological changes in organs and tissues in chronic fluoride intoxication (literature review)https://orcid.org/0000-0003-3692-2616БугаеваМария СергеевнаBugaevaMaria S.

Канд. биол. наук, ст. науч. сотр. лаб. молекулярно-генетических и экспериментальных исследований ФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний», 654041, Новокузнецк.

e-mail: bugms14@mail.ru

MD, PhD, senior researcher of the molecular-genetic and experimental study laboratory, Research Institute for Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk, 654041, Russian Federation.

e-mail: bugms14@mail.ru

bugms14@mail.ruhttps://orcid.org/0000-0001-8292-4810КазицкаяАнастасия С.KazitskayaAnastasiya S.noemail@neicon.ruhttps://orcid.org/0000-0001-7008-1035ЯдыкинаТатьяна К.YadykinaTatyana K.noemail@neicon.ruhttps://orcid.org/0000-0002-4797-7842ЖуковаАнна Г.ZhukovaAnna G.noemail@neicon.ruhttps://orcid.org/0000-0002-1127-6980МихайловаНадежда Н.MikhailovaNadezhda N.noemail@neicon.ruФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний»; Новокузнецкий государственный институт усовершенствования врачей — филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияResearch Institute for Complex Problems of Hygiene and Occupational Diseases; Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian FederationRussian FederationФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний»РоссияResearch Institute for Complex Problems of Hygiene and Occupational DiseasesRussian Federation2023310820231027700705Copyright © Бугаева М.С., Казицкая А.С., Ядыкина Т.К., Жукова А.Г., Михайлова Н.Н., 20232023Бугаева М.С., Казицкая А.С., Ядыкина Т.К., Жукова А.Г., Михайлова Н.Н.Bugaeva M.S., Kazitskaya A.S., Yadykina T.K., Zhukova A.G., Mikhailova N.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.rjhas.ru/jour/article/view/3274Введение

Введение. Традиционно основным проявлением хронической фтористой интоксикации считается поражение костной системы, однако в последние годы опубликованы работы, посвящённые изучению механизма действия фтора и его соединений на нескелетные ткани. На основе анализа баз данных РИНЦ, PubMed, Scopus, Web of Science, MedLine, Google Scholar, CyberLeninka представлен обзор современных представлений о морфологических изменениях органов и систем в условиях длительного воздействия на организм соединений фтора.

Влияние фтора на опорно-двигательный аппарат. Показано, что фтор индуцирует дифференцировку и апоптоз остеобластов и остеокластов, приводя к разнообразным повреждениям скелета. Активный остеогенез и ускоренный костный обмен являются ключевыми процессами в прогрессировании флюороза скелета и патологической основой разнообразия остеогенных поражений.

Влияние фтора на нескелетные ткани. Приведены данные о влиянии фтора на индукцию свободнорадикального окисления в коре головного мозга, перераспределение и повреждение нервных клеток. В сердечной мышце показана активация апоптоза, окислительного стресса и снижение активности антиоксидантных ферментов при воздействии фторида натрия, подтверждено развитие функциональных и структурных нарушений в миокарде. Фтористой интоксикацией обусловлено формирование дегенеративных и воспалительных изменений дыхательной системы, печени и почек, структурных нарушений и дисфункции щитовидной железы, а также повышение уровня активных форм кислорода и индукция апоптоза в этих органах. Приведены данные о воздействии фторида натрия на гистологическую структуру репродуктивных органов, сопровождающемся снижением подвижности сперматозоидов, отсутствием дифференцировки и созревания сперматоцитов, интенсификацией свободнорадикального окисления и апоптоза клеток.

Заключение

Заключение. Проведённый анализ позволяет расширить представление о патогенетических основах морфологических изменений и функциональной несостоятельности органов и тканей в условиях хронической фтористой интоксикации для обоснования системного, комплексного подхода к её лечению и профилактике.

Участие авторов

Участие авторов:Бугаева М.С. — концепция и дизайн исследования, сбор и обработка материала, написание текста;Казицкая А.С., Ядыкина Т.К. — сбор и обработка материала;Жукова А.Г. — сбор и обработка материала, редактирование текста;Михайлова Н.Н. — концепция исследования, редактирование текста.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Поступила

Поступила: 23.03.2023 / Принята к печати: 07.06.2023 / Опубликовано: 30.08.2023

Introduction

Introduction. Traditionally, the main manifestation of chronic fluoride intoxication is the damage to the skeletal system, while during recent years a large amount of works has been accumulated on the study of the mechanism of action of both fluorine and its compounds on non-skeletal tissues. Based on the analysis of the Russian Science Citation Index, PubMed, Scopus, Web of Science, MedLine, Google Scholar, CyberLeninka databases, a review of contemporary concepts of morphological changes in organs and systems under the conditions of long-term exposure to fluorine compounds is presented.

Effect of fluorine on the musculoskeletal system. Fluorine Ihas been shown to induce differentiation and apoptosis of osteoblasts and osteoclasts, leading to various skeletal injuries. Active osteogenesis and accelerated bone metabolism are key processes in the progression of skeletal fluorosis and the pathological base of the diversity of osteogenic lesions.

Effect of fluorine on non-skeletal tissues. Data on the effect of fluorine on the induction of free radical oxidation in the cerebral cortex, redistribution, and damage to nerve cells are presented. Activation of apoptosis, oxidative stress, and a decrease in the activity of antioxidant enzymes under the influence of sodium fluoride in the heart muscle are shown, data on the development of functional and structural disorders in the myocardium are given. Due to fluoride intoxication, the formation of degenerative and inflammatory changes in the respiratory system, liver, and kidneys, structural disorders and dysfunction of the thyroid gland, as well as an increase in the level of reactive oxygen species and the induction of apoptosis in these organs are shown. Data on the effect of sodium fluoride on the histological structure of the reproductive organs with a decrease in sperm motility, lack of differentiation and maturation of spermatocytes, intensification of free radical oxidation and cell apoptosis are presented.

Conclusion

Conclusion. The analysis carried out allows expanding the understanding of the pathogenetic bases of morphological changes and functional failure of organs and tissues under the conditions of chronic fluoride intoxication, to substantiate a systemic, integrated approach to its treatment and prevention.

Contribution

Contribution:Bugaeva M.S. — concept and design of the study, collection and processing of material, writing a text;Kazitskaya A.S., Yadykina T.K. — collection and processing of material;Zhukova A.G. — collection and processing of material, text editing;Mikhailova N.N. — concept of the study, text editing.All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest

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

Acknowledgement

Acknowledgement. The study had no sponsorship.

Received

Received: March 23, 2023 / Accepted: June 7, 2023 / Published: August 30, 2023

хроническая фтористая интоксикацияморфологические изменениявнутриклеточные сигнальные путиапоптозобзорchronic fluoride intoxicationmorphological changesintracellular signaling pathwaysapoptosisreviewReferencesZhao Y.Y. The progress about the influence of fluorine on bone. Med. Recapitul. 2006; 12: 1092–4.Zhao Y.Y. The progress about the influence of fluorine on bone. Med. Recapitul. 2006; 12: 1092–4.Шалина Т.И., Васильева Л.С. Общие вопросы токсического действия фтора. Сибирский медицинский журнал (Иркутск). 2009; 88(5): 5–9. https://elibrary.ru/kzbtilShalina T.I., Vasil’eva L.S. General problems of toxic effect of fluorine. Sibirskiy meditsinskiy zhurnal (Irkutsk). 2009; 88(5): 5–9. https://elibrary.ru/kzbtil (in Russian)Barbier O., Arreola-Mendoza L., Del Razo L.M. Molecular mechanisms of fluoride toxicity. Chem. Biol. Interact. 2010; 188(2): 319–33. https://doi.org/10.1016/j.cbi.2010.07.011Barbier O., Arreola-Mendoza L., Del Razo L.M. Molecular mechanisms of fluoride toxicity. Chem. Biol. Interact. 2010; 188(2): 319–33. https://doi.org/10.1016/j.cbi.2010.07.011Янин Е.П. Фтор в питьевых водах города Саранска и его гигиеническое значение. М.; 1996.Yanin E.P. Fluorine in the Drinking Waters of the City of Saransk and Its Hygienic Significance [Ftor v pit’evykh vodakh goroda Saranska i ego gigienicheskoe znachenie]. Moscow; 1996. (in Russian)Измеров Н.Ф., Бухтияров И.В., Прокопенко Л.В., Кузьмина Л.П., Соркина Н.С., Бурмистрова Т.Б. и др. Современные аспекты сохранения и укрепления здоровья работников, занятых на предприятиях по производству алюминия. Медицина труда и промышленная экология. 2012; 52(11): 1–7. https://elibrary.ru/pihqkdIzmerov N.F., Bukhtiyarov I.V., Prokopenko L.V., Kuz’mina L.P., Sorkina N.S., Burmistrova T.B., et al. Contemporary aspects of maintenance and promotion of health of the workers employed at the aluminum production enterprises. Meditsina truda i promyshlennaya ekologiya. 2012; 52(11): 1–7. https://elibrary.ru/pihqkd (in Russian)Qiao L., Liu X., He Y., Zhang J., Huang H., Bian W., et al. Progress of signaling pathways, stress pathways and epigenetics in the pathogenesis of skeletal fluorosis. Int. J. Mol. Sci. 2021; 22(21): 11932. https://doi.org/10.3390/ijms222111932Qiao L., Liu X., He Y., Zhang J., Huang H., Bian W., et al. Progress of signaling pathways, stress pathways and epigenetics in the pathogenesis of skeletal fluorosis. Int. J. Mol. Sci. 2021; 22(21): 11932. https://doi.org/10.3390/ijms222111932Cicek E., Aydin G., Akdogan M., Okutan H. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum. Exp. Toxicol. 2005; 24(2): 79–87. https://doi.org/10.1191/0960327105ht505oaCicek E., Aydin G., Akdogan M., Okutan H. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum. Exp. Toxicol. 2005; 24(2): 79–87. https://doi.org/10.1191/0960327105ht505oaWei W., Pang S.J., Sun D.J. The pathogenesis of endemic fluorosis: Research progress in the last 5 years. J. Cell Mol. Med. 2019; 23(4): 2333–42. https://doi.org/10.1111/jcmm.14185Wei W., Pang S.J., Sun D.J. The pathogenesis of endemic fluorosis: Research progress in the last 5 years. J. Cell Mol. Med. 2019; 23(4): 2333–42. https://doi.org/10.1111/jcmm.14185Boivin G., Chavassieux P., Chapuy M.C., Baud C.A., Meunier P.J. Skeletal fluorosis: Histomorphometric findings. J. Bone Miner. Res. 1990; 5(S1): 185–9. https://doi.org/10.1002/jbmr.5650051382Boivin G., Chavassieux P., Chapuy M.C., Baud C.A., Meunier P.J. Skeletal fluorosis: Histomorphometric findings. J. Bone Miner. Res. 1990; 5(S1): 185–9. https://doi.org/10.1002/jbmr.5650051382Huo L., Liu K., Pei J., Yang Y., Ye Y., Liu Y., et al. Fluoride promotes viability and differentiation of osteoblast-like Saos-2 cells via BMP/Smads signaling pathway. Biol. Trace Elem. Res. 2013; 155(1): 142–9. https://doi.org/10.1007/s12011-013-9770-0Huo L., Liu K., Pei J., Yang Y., Ye Y., Liu Y., et al. Fluoride promotes viability and differentiation of osteoblast-like Saos-2 cells via BMP/Smads signaling pathway. Biol. Trace Elem. Res. 2013; 155(1): 142–9. https://doi.org/10.1007/s12011-013-9770-0Wang Y., Zhang X., Zhao Z., Xu H. Preliminary analysis of MicroRNAs expression profiling in MC3T3-E1 cells exposed to fluoride. Biol. Trace Elem. Res. 2017; 176(2): 367–73. https://doi.org/10.1007/s12011-016-0833-xWang Y., Zhang X., Zhao Z., Xu H. Preliminary analysis of MicroRNAs expression profiling in MC3T3-E1 cells exposed to fluoride. Biol. Trace Elem. Res. 2017; 176(2): 367–73. https://doi.org/10.1007/s12011-016-0833-xLi X.N., Lv P., Sun Z., Li G.S., Xu H. Role of unfolded protein response in affecting osteoblast differentiation induced by fluoride. Biol. Trace Elem. Res. 2014; 158(1): 113–21. https://doi.org/10.1007/s12011-014-9897-7Li X.N., Lv P., Sun Z., Li G.S., Xu H. Role of unfolded protein response in affecting osteoblast differentiation induced by fluoride. Biol. Trace Elem. Res. 2014; 158(1): 113–21. https://doi.org/10.1007/s12011-014-9897-7Yan X., Tian X., Wang L., Zhou W., Zhang W., Lv Y., et al. Fluoride induces apoptosis in MC3T3-E1 osteoblasts by altering ROS levels and mitochondrial membrane potentials. Fluoride. 2017; 50(2): 213–22.Yan X., Tian X., Wang L., Zhou W., Zhang W., Lv Y., et al. Fluoride induces apoptosis in MC3T3-E1 osteoblasts by altering ROS levels and mitochondrial membrane potentials. Fluoride. 2017; 50(2): 213–22.Wang Y., Duan X.Q., Zhao Z.T., Zhang X.Y., Wang H., Liu D.W., et al. Fluoride affects calcium homeostasis by regulating parathyroid hormone, PTH-related peptide, and calcium-sensing receptor expression. Biol. Trace Elem. Res. 2015; 165(2): 159–66. https://doi.org/10.1007/s12011-015-0245-3Wang Y., Duan X.Q., Zhao Z.T., Zhang X.Y., Wang H., Liu D.W., et al. Fluoride affects calcium homeostasis by regulating parathyroid hormone, PTH-related peptide, and calcium-sensing receptor expression. Biol. Trace Elem. Res. 2015; 165(2): 159–66. https://doi.org/10.1007/s12011-015-0245-3Yu X., Yu H., Jiang N., Zhang X., Zhang M., Xu H. PTH (1-34) affects bone turnover governed by osteocytes exposed to fluoride. Toxicol. Lett. 2018; 288: 25–34. https://doi.org/10.1016/j.toxlet.2018.02.014Yu X., Yu H., Jiang N., Zhang X., Zhang M., Xu H. PTH (1-34) affects bone turnover governed by osteocytes exposed to fluoride. Toxicol. Lett. 2018; 288: 25–34. https://doi.org/10.1016/j.toxlet.2018.02.014Жукова А.Г., Михайлова Н.Н., Ядыкина Т.К., Алехина Д.А., Горохова Л.Г., Романенко Д.В. и др. Экспериментальные исследования внутриклеточных защитных механизмов печени в развитии хронической фтористой интоксикации. Медицина труда и промышленная экология. 2016; 56(5): 21–4. https://elibrary.ru/vwgxgvZhukova A.G., Mikhaylova N.N., Yadykina T.K., Alekhina D.A., Gorokhova L.G., Romanenko D.V., et al. Experimental studies of intracellular liver protective mechanisms in development of chronic fluorine intoxication. Meditsina truda i promyshlennaya ekologiya. 2016; 56(5): 21–4. https://elibrary.ru/vwgxgv (in Russian)Бугаева М.С., Бондарев О.И., Горохова Л.Г., Кизиченко Н.В., Жданова Н.Н. Экспериментальное изучение специфичности развития морфологических изменений внутренних органов при длительном воздействии на организм угольно-породной пыли и фторида натрия. Медицина труда и промышленная экология. 2022; 62(5): 285–94. https://doi.org/10.31089/1026-9428-2022-62-5-285-294 https://elibrary.ru/akcvekBugaeva M.S., Bondarev O.I., Gorokhova L.G., Kizichenko N.V., Zhdanova N.N. Experimental study of the specificity of morphological changes development in internal organs with prolonged exposure to coal-rock dust and sodium fluoride to the body. Meditsina truda i promyshlennaya ekologiya. 2022; 62(5): 285–94. https://doi.org/10.31089/1026-9428-2022-62-5-285-294 https://elibrary.ru/akcvek (in Russian)Yan L., Liu S., Wang C., Wang F., Song Y., Yan N., et al. JNK and NADPH oxidase involved in fluoride-induced oxidative stress in BV-2 microglia cells. Mediators Inflamm. 2013; 2013: 895975. https://doi.org/10.1155/2013/895975Yan L., Liu S., Wang C., Wang F., Song Y., Yan N., et al. JNK and NADPH oxidase involved in fluoride-induced oxidative stress in BV-2 microglia cells. Mediators Inflamm. 2013; 2013: 895975. https://doi.org/10.1155/2013/895975Lou D.D., Guan Z.Z., Liu Y.J., Liu Y.F., Zhang K.L., Pan J.G., et al. The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain. Arch. Toxicol. 2013; 87(3): 449–57. https://doi.org/10.1007/s00204-012-0942-zLou D.D., Guan Z.Z., Liu Y.J., Liu Y.F., Zhang K.L., Pan J.G., et al. The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain. Arch. Toxicol. 2013; 87(3): 449–57. https://doi.org/10.1007/s00204-012-0942-zXu Z., Xu B., Xia T., He W., Gao P., Guo L., et al. Relationship between intracellular Ca2+ and ROS during fluoride-induced injury in SH-SY5Y cells. Environ. Toxicol. 2013; 28(6): 307–12. https://doi.org/10.1002/tox.20721Xu Z., Xu B., Xia T., He W., Gao P., Guo L., et al. Relationship between intracellular Ca2+ and ROS during fluoride-induced injury in SH-SY5Y cells. Environ. Toxicol. 2013; 28(6): 307–12. https://doi.org/10.1002/tox.20721Wei N., Dong Y.T., Deng J., Wang Y., Qi X.L., Yu W.F., et al. Changed expressions of N-methyl-d-aspartate receptors in the brains of rats and primary neurons exposed to high level of fluoride. J. Trace Elem. Med. Biol. 2018; 45: 31–40. https://doi.org/10.1016/j.jtemb.2017.09.020Wei N., Dong Y.T., Deng J., Wang Y., Qi X.L., Yu W.F., et al. Changed expressions of N-methyl-d-aspartate receptors in the brains of rats and primary neurons exposed to high level of fluoride. J. Trace Elem. Med. Biol. 2018; 45: 31–40. https://doi.org/10.1016/j.jtemb.2017.09.020Agalakova N.I., Nadei O.V. Inorganic fluoride and functions of brain. Crit. Rev. Toxicol. 2020; 50(1): 28–46. https://doi.org/10.1080/10408444.2020.1722061Agalakova N.I., Nadei O.V. Inorganic fluoride and functions of brain. Crit. Rev. Toxicol. 2020; 50(1): 28–46. https://doi.org/10.1080/10408444.2020.1722061Grandjean P. Developmental fluoride neurotoxicity: an updated review. Environ. Health. 2019; 18(1): 110. https://doi.org/10.1186/s12940-019-0551-xGrandjean P. Developmental fluoride neurotoxicity: an updated review. Environ. Health. 2019; 18(1): 110. https://doi.org/10.1186/s12940-019-0551-xKurdi M.S. Chronic fluorosis: The disease and its anaesthetic implications. Indian J. Anaesth. 2016; 60(3): 157–62. https://doi.org/10.4103/0019-5049.177867Kurdi M.S. Chronic fluorosis: The disease and its anaesthetic implications. Indian J. Anaesth. 2016; 60(3): 157–62. https://doi.org/10.4103/0019-5049.177867Reddy Y.P., Tiwari S., Tomar L.K., Desai N., Sharma V.K. Fluoride-induced expression of neuroinflammatory markers and neurophysiological regulation in the brain of Wistar rat model. Biol. Trace Elem. Res. 2021; 199(7): 2621–6. https://doi.org/10.1007/s12011-020-02362-xReddy Y.P., Tiwari S., Tomar L.K., Desai N., Sharma V.K. Fluoride-induced expression of neuroinflammatory markers and neurophysiological regulation in the brain of Wistar rat model. Biol. Trace Elem. Res. 2021; 199(7): 2621–6. https://doi.org/10.1007/s12011-020-02362-xAbdelaleem M.M., El-Tahawy N.F.G., Abozaid S.M.M., Abdel-Hakim S.A. Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: Light and electron microscopic study. Endocr. Regul. 2018; 52(2): 59–68. https://doi.org/10.2478/enr-2018-0007Abdelaleem M.M., El-Tahawy N.F.G., Abozaid S.M.M., Abdel-Hakim S.A. Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: Light and electron microscopic study. Endocr. Regul. 2018; 52(2): 59–68. https://doi.org/10.2478/enr-2018-0007Liu H.L., Zeng Q., Cui Y.S., Zhang L., Fu G., Hou C.C., et al. Fluoride-induced thyroid cell apoptosis. Fluoride. 2014; 47(2): 161–9.Liu H.L., Zeng Q., Cui Y.S., Zhang L., Fu G., Hou C.C., et al. Fluoride-induced thyroid cell apoptosis. Fluoride. 2014; 47(2): 161–9.Jiang Y., Guo X., Sun Q., Shan Z., Teng W. Effects of excess fluoride and iodide on thyroid function and morphology. Biol. Trace Elem. Res. 2016; 170(2): 382–9. https://doi.org/10.1007/s12011-015-0479-0Jiang Y., Guo X., Sun Q., Shan Z., Teng W. Effects of excess fluoride and iodide on thyroid function and morphology. Biol. Trace Elem. Res. 2016; 170(2): 382–9. https://doi.org/10.1007/s12011-015-0479-0Ядыкина Т.К., Бугаева М.С., Кочергина Т.В., Михайлова Н.Н. Клинико-экспериментальные исследования влияния хронической фтористой интоксикации на гормональный статус организма и морфологические изменения щитовидной железы. Медицина труда и промышленная экология. 2021; 61(3): 173–80. https://doi.org/10.31089/1026-9428-2021-61-3-173-180 https://elibrary.ru/bpwqqxYadykina T.K., Bugaeva M.S., Kochergina T.V., Mikhaylova N.N. Clinical and experimental studies of the effect of chronic fluoride intoxication on the hormonal status of the body and morphological changes in the thyroid gland. Meditsina truda i promyshlennaya ekologiya. 2021; 61(3): 173–80. https://doi.org/10.31089/1026-9428-2021-61-3-173-180 https://elibrary.ru/bpwqqx (in Russian)Hassan N.H., Amin M.A. Resveratrol thyro-protective role in fluorosis rat model (histo-morphometric, biochemical and ultrastructural study). Tissue Cell. 2023; 80: 101986. https://doi.org/10.1016/j.tice.2022.101986Hassan N.H., Amin M.A. Resveratrol thyro-protective role in fluorosis rat model (histo-morphometric, biochemical and ultrastructural study). Tissue Cell. 2023; 80: 101986. https://doi.org/10.1016/j.tice.2022.101986Skórka-Majewicz M., Goschorska M., Żwierełło W., Baranowska-Bosiacka I., Styburski D., Kapczuk P., et al. Effect of fluoride on endocrine tissues and their secretory functions – review. Chemosphere. 2020; 260: 127565. https://doi.org/10.1016/j.chemosphere.2020.127565Skórka-Majewicz M., Goschorska M., Żwierełło W., Baranowska-Bosiacka I., Styburski D., Kapczuk P., et al. Effect of fluoride on endocrine tissues and their secretory functions – review. Chemosphere. 2020; 260: 127565. https://doi.org/10.1016/j.chemosphere.2020.127565Chen Q., Chai Y.C., Mazumder S., Jiang C., Macklis R.M., Chisolm G.M., et al. The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Diff. 2003; 10(3): 323–34. https://doi.org/10.1038/sj.cdd.4401148Chen Q., Chai Y.C., Mazumder S., Jiang C., Macklis R.M., Chisolm G.M., et al. The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Diff. 2003; 10(3): 323–34. https://doi.org/10.1038/sj.cdd.4401148Panneerselvam L., Govindarajan V., Ameeramja J., Nair H.R., Perumal E. Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats. Biochimie. 2015; 119: 27–35. https://doi.org/10.1016/j.biochi.2015.10.002Panneerselvam L., Govindarajan V., Ameeramja J., Nair H.R., Perumal E. Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats. Biochimie. 2015; 119: 27–35. https://doi.org/10.1016/j.biochi.2015.10.002Gutowska I., Baranowska-Bosiacha I., Baśkiewicz M., Milo B., Siennicka A., Marchiewicz M., et al. Fluoride as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells. Toxicol. Lett. 2010; 196(2): 74–9. https://doi.org/10.1016/j.toxlet.2010.03.1167Gutowska I., Baranowska-Bosiacha I., Baśkiewicz M., Milo B., Siennicka A., Marchiewicz M., et al. Fluoride as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells. Toxicol. Lett. 2010; 196(2): 74–9. https://doi.org/10.1016/j.toxlet.2010.03.1167Flora S.J., Pachauri V., Mittal M., Kumar D. Interactive effect of arsenic and fluoride on cardio-respiratory disorders in male rats: possible role of reactive oxygen species. Biometals. 2011; 24(4): 615–28. https://doi.org/10.1007/s10534-011-9412-yFlora S.J., Pachauri V., Mittal M., Kumar D. Interactive effect of arsenic and fluoride on cardio-respiratory disorders in male rats: possible role of reactive oxygen species. Biometals. 2011; 24(4): 615–28. https://doi.org/10.1007/s10534-011-9412-yMa Y., Niu R., Sun Z., Wang J., Luo G., Zhang J., et al. Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta. Arch. Toxicol. 2012; 86(6): 849–56. https://doi.org/10.1007/s00204-012-0803-9Ma Y., Niu R., Sun Z., Wang J., Luo G., Zhang J., et al. Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta. Arch. Toxicol. 2012; 86(6): 849–56. https://doi.org/10.1007/s00204-012-0803-9Namiki M., Kawashima S., Yamashita T., Ozaki M., Hirase T., Ishida T., et al. Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: synergism with hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 2002; 22(1): 115–20. https://doi.org/10.1161/hq0102.102278Namiki M., Kawashima S., Yamashita T., Ozaki M., Hirase T., Ishida T., et al. Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: synergism with hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 2002; 22(1): 115–20. https://doi.org/10.1161/hq0102.102278Afolabi O.K., Oyewo E.B., Adekunle A.S., Adedosu O.T., Adedeji A.L. Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats. Arh. Hig. Rada Toksikol. 2013; 64(4): 521–9. https://doi.org/10.2478/10004-1254-64-2013-2351Afolabi O.K., Oyewo E.B., Adekunle A.S., Adedosu O.T., Adedeji A.L. Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats. Arh. Hig. Rada Toksikol. 2013; 64(4): 521–9. https://doi.org/10.2478/10004-1254-64-2013-2351Ji F., Xu H., Zhang Y.X., Zhang J., Liu W.Y., Shao H., et al. Study on the cardiovascular system damage in skeletal fluorosis patients. Chin. J. Ctrl. Endem. Dis. 2004; 19(6): 321–6.Ji F., Xu H., Zhang Y.X., Zhang J., Liu W.Y., Shao H., et al. Study on the cardiovascular system damage in skeletal fluorosis patients. Chin. J. Ctrl. Endem. Dis. 2004; 19(6): 321–6.Liao W., Guan Z.Z., Liu Y.F., Xu S.Q., Wu C.X., Li Y., et al. Observations on electrocardiograms in a population living in a region with coal-burning-borne endemic fluorosis after comprehensive controls. Chin. J. Endemiol. 2013; 32(4): 424–6.Liao W., Guan Z.Z., Liu Y.F., Xu S.Q., Wu C.X., Li Y., et al. Observations on electrocardiograms in a population living in a region with coal-burning-borne endemic fluorosis after comprehensive controls. Chin. J. Endemiol. 2013; 32(4): 424–6.Basha M.P., Sujitha N.S. Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats. Toxicol. Int. 2011; 18(2): 99–104. https://doi.org/10.4103/0971-6580.84260Basha M.P., Sujitha N.S. Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats. Toxicol. Int. 2011; 18(2): 99–104. https://doi.org/10.4103/0971-6580.84260Viragh E., Viragh H., Laczka J., Coldea V. Health effects of occupational exposure to fluorine and its compounds in a small-scale enterprise. Ind. Health. 2006; 44(1): 64–8. https://doi.org/10.2486/indhealth.44.64Viragh E., Viragh H., Laczka J., Coldea V. Health effects of occupational exposure to fluorine and its compounds in a small-scale enterprise. Ind. Health. 2006; 44(1): 64–8. https://doi.org/10.2486/indhealth.44.64Thrane E.V., Refsnes M., Thoresen G.H., Låg M., Schwarze P.E. Fluoride-induced apoptosis in epithelial lung cells involves activation of MAP kinases p38 and possibly JNK. Toxicol. Sci. 2001; 61(1): 83–91. https://doi.org/10.1093/toxsci/61.1.83Thrane E.V., Refsnes M., Thoresen G.H., Låg M., Schwarze P.E. Fluoride-induced apoptosis in epithelial lung cells involves activation of MAP kinases p38 and possibly JNK. Toxicol. Sci. 2001; 61(1): 83–91. https://doi.org/10.1093/toxsci/61.1.83Perera T., Ranasinghe S., Alles N., Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environ. Health Prev. Med. 2018; 23(1): 17. https://doi.org/10.1186/s12199-018-0707-2Perera T., Ranasinghe S., Alles N., Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environ. Health Prev. Med. 2018; 23(1): 17. https://doi.org/10.1186/s12199-018-0707-2Song G.H., Huang F.B., Gao J.P., Liu M.L., Pang W.B., Li Wb., et al. Effects of fluoride on DNA damage and caspase-mediated apoptosis in the liver of rats. Biol. Trace Elem. Res. 2015; 166(2): 173–82. https://doi.org/10.1007/s12011-015-0265-zSong G.H., Huang F.B., Gao J.P., Liu M.L., Pang W.B., Li Wb., et al. Effects of fluoride on DNA damage and caspase-mediated apoptosis in the liver of rats. Biol. Trace Elem. Res. 2015; 166(2): 173–82. https://doi.org/10.1007/s12011-015-0265-zThangapandiyan S.M., Miltonprabu S. Ameliorative effect of epigallocatechin gallate on sodium fluoride induced oxidative stress mediated metabolism in rat. Int. J. Pharmacol. Toxicol. 2014; 2(2): 76–85. https://doi.org/10.14419/ijpt.v2i2.3010Thangapandiyan S.M., Miltonprabu S. Ameliorative effect of epigallocatechin gallate on sodium fluoride induced oxidative stress mediated metabolism in rat. Int. J. Pharmacol. Toxicol. 2014; 2(2): 76–85. https://doi.org/10.14419/ijpt.v2i2.3010Luo Q., Cui H., Deng H., Kuang P., Liu H., Lu Y., et al. Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride. Oncotarget. 2017; 8(31): 50430–46. https://doi.org/10.18632/oncotarget.17365Luo Q., Cui H., Deng H., Kuang P., Liu H., Lu Y., et al. Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride. Oncotarget. 2017; 8(31): 50430–46. https://doi.org/10.18632/oncotarget.17365Omóbòwálé T.O., Oyagbemi A.A., Alaba B.A., Ola-Davies O.E., Adejumobi O.A., Asenuga E.R., et al. Ameliorative effect of Azadirachta indica on sodium fluoride-induced hypertension through improvement of antioxidant defence system and upregulation of extracellular signal regulated kinase 1/2 signaling. J. Basic Clin. Physiol. Pharmacol. 2018; 29(2): 155–64. https://doi.org/10.1515/jbcpp-2017-0029Omóbòwálé T.O., Oyagbemi A.A., Alaba B.A., Ola-Davies O.E., Adejumobi O.A., Asenuga E.R., et al. Ameliorative effect of Azadirachta indica on sodium fluoride-induced hypertension through improvement of antioxidant defence system and upregulation of extracellular signal regulated kinase 1/2 signaling. J. Basic Clin. Physiol. Pharmacol. 2018; 29(2): 155–64. https://doi.org/10.1515/jbcpp-2017-0029Wei Q., Deng, H., Cui H., Fang J., Zuo Z., Deng J., et al. A mini review of fluoride-induced apoptotic pathways. Environ. Sci. Pollut. Res. 2018; 25(34): 33926–35. https://doi.org/10.1007/s11356-018-3406-zWei Q., Deng, H., Cui H., Fang J., Zuo Z., Deng J., et al. A mini review of fluoride-induced apoptotic pathways. Environ. Sci. Pollut. Res. 2018; 25(34): 33926–35. https://doi.org/10.1007/s11356-018-3406-zZhang Z., Zhou B., Wang H., Wang F., Song Y., Liu S., et al. Maize purple plant pigment protects against fluoride-induced oxidative damage of liver and kidney in rats. Int. J. Environ. Res. Public Health. 2014; 11(1): 1020–33. https://doi.org/10.3390/ijerph110101020Zhang Z., Zhou B., Wang H., Wang F., Song Y., Liu S., et al. Maize purple plant pigment protects against fluoride-induced oxidative damage of liver and kidney in rats. Int. J. Environ. Res. Public Health. 2014; 11(1): 1020–33. https://doi.org/10.3390/ijerph110101020Chattopadhyay A., Podder S., Agarwal S., Bhattacharya S. Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice. Arch. Toxicol. 2011; 85(4): 327–35. https://doi.org/10.1007/s00204-010-0588-7Chattopadhyay A., Podder S., Agarwal S., Bhattacharya S. Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice. Arch. Toxicol. 2011; 85(4): 327–35. https://doi.org/10.1007/s00204-010-0588-7Kim J., Kwon W.S., Rahman M.S., Lee J.S., Yoon S.J., Park Y.J., et al. Effect of sodium fluoride on male mouse fertility. Andrology. 2015; 3(3): 544–51. https://doi.org/10.1111/andr.12006Kim J., Kwon W.S., Rahman M.S., Lee J.S., Yoon S.J., Park Y.J., et al. Effect of sodium fluoride on male mouse fertility. Andrology. 2015; 3(3): 544–51. https://doi.org/10.1111/andr.12006Tian Y., Xiao Y., Wang B., Sun C., Tang K., Sun F. Vitamin E and lycopene reduce coal burning fluorosis-induced spermatogenic cell apoptosis via oxidative stress-mediated JNK and ERK signaling pathways. Biosci. Rep. 2017; 38(4): BSR20171003. https://doi.org/10.1042/BSR20171003Tian Y., Xiao Y., Wang B., Sun C., Tang K., Sun F. Vitamin E and lycopene reduce coal burning fluorosis-induced spermatogenic cell apoptosis via oxidative stress-mediated JNK and ERK signaling pathways. Biosci. Rep. 2017; 38(4): BSR20171003. https://doi.org/10.1042/BSR20171003Kumar N., Sood S., Arora B., Singh M., Beena. Effect of duration of fluoride exposure on the reproductive system in male rabbits. J. Hum. Reprod. Sci. 2010; 3(3): 148–52. https://doi.org/10.4103/0974-1208.74159Kumar N., Sood S., Arora B., Singh M., Beena. Effect of duration of fluoride exposure on the reproductive system in male rabbits. J. Hum. Reprod. Sci. 2010; 3(3): 148–52. https://doi.org/10.4103/0974-1208.74159Zhao M.X., Zhou G.Y., Zhu J.Y., Gong B., Hou J.X., Zhou T., et al. Fluoride exposure, follicle stimulating hormone receptor gene polymorphism and hypothalamus-pituitary-ovarian axis hormones in Chinese women. Biomed. Environ. Sci. 2015; 28(9): 696–700. https://doi.org/10.3967/bes2015.099Zhao M.X., Zhou G.Y., Zhu J.Y., Gong B., Hou J.X., Zhou T., et al. Fluoride exposure, follicle stimulating hormone receptor gene polymorphism and hypothalamus-pituitary-ovarian axis hormones in Chinese women. Biomed. Environ. Sci. 2015; 28(9): 696–700. https://doi.org/10.3967/bes2015.099Wang H.W., Zhao W.P., Tan P.P., Liu J., Zhao J., Zhou B.H. The MMP-9/TIMP-1 system is involved in fluoride-induced reproductive dysfunctions in female mice. Biol. Trace Elem. Res. 2017; 178(2): 253–60. https://doi.org/10.1007/s12011-016-0929-3Wang H.W., Zhao W.P., Tan P.P., Liu J., Zhao J., Zhou B.H. The MMP-9/TIMP-1 system is involved in fluoride-induced reproductive dysfunctions in female mice. Biol. Trace Elem. Res. 2017; 178(2): 253–60. https://doi.org/10.1007/s12011-016-0929-3Yin S., Song C., Wu H., Chen X., Zhang Y. Adverse effects of high concentrations of fluoride on characteristics of the ovary and mature oocyte of mouse. PLoS One. 2015; 10(6): e0129594. https://doi.org/10.1371/journal.pone.0129594Yin S., Song C., Wu H., Chen X., Zhang Y. Adverse effects of high concentrations of fluoride on characteristics of the ovary and mature oocyte of mouse. PLoS One. 2015; 10(6): e0129594. https://doi.org/10.1371/journal.pone.0129594

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