Metal nano- and microparticles-induced oral mucosa immunopathological inflammation


DOI: https://dx.doi.org/10.18565/therapy.2024.2.78-91

Labis V.V., Bazikyan E.A., Sizova S.V., Khaidukov S.V., Zhigalina O.M., Khmelenin D.N., Dyachkova I.G., Zolotov D.A., Asadchikov V.E., Isakina M.O., Gildeeva G.N., Kozlov I.G.

1) Russian University of Medicine of the Ministry of Healthcare of Russia, Moscow; 2) Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of RAS, Moscow; 3) National Research Center “Kurchatov Institute”, Moscow; 4) I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)
Abstract. Studies of the causes and mechanisms of development of oral mucosa chronic inflammation must be carried out taking into account immunological and nanotechnological aspects that fully reflect the picture of cause-effect relations.
The aim: To analyze a clinical case to verify the cause-effect relations in the pathogenesis of idiopathic immunopathological inflammation of oral mucosa induced by metal nano- and microparticles (NMMPs).
Material and methods. In order to verify the main diagnosis in patient Zh., 80 years old, after complex implantological treatment (at the age of 70 years) and the appearance of the first clinical signs of idiopathic immunopathological chronic inflammation of the oral mucosa, clinical and laboratory studies were performed, which made it possible to identify a new etiopathogenetic link of cause-effect relations of arisen complications. During surgical revisions of the area of previously installed dental implants and metal bar structures, histology of biopsy samples of the oral mucosa and bone structures was performed to identify impregnated NMMPs into the structure of pathologically changed tissues. In addition, a basophil test was performed for the presence of delayed-type hypersensitivity with NMMPs-containing supernatants obtained from the surface of the bar structure and dental implants.
Results. The identity of metal NMMPs that impregnated pathological tissue areas with the presence of a chronic inflammatory process and supernatants obtained from the surface of medical devices in laboratory conditions, which were previously installed in the patient’s oral cavity, was found. No delayed allergic reaction to nano-sized particles was fixed.
Conclusion. One of the reasons for oral mucosa chronic autoinflammation occurrence may be the emission and accumulation of metal NMMRs from the surface of medical alloys used in the oral cavity of patients.

Literature


1. Gao Y., Ye Y., Wang J. et al. Effects of titanium dioxide nanoparticles on nutrient absorption and metabolism in rats: Distinguishing the susceptibility of amino acids, metal elements, and glucose. Nanotoxicology. 2020; 14(10): 1301–23.


https://doi.org/10.1080/17435390.2020.1817597. PMID: 32930049.


2. Cao X., Han Y., Gu M. et al. Foodborne titanium dioxide nanoparticles induce stronger adverse effects in obese mice than non-obese mice: Gut microbiota dysbiosis, colonic inflammation, and proteome alterations. Small. 2020; 16(36): e2001858.


https://doi.org/10.1002/smll.202001858. PMID: 32519440.


3. Лабис В.В., Базикян Э.А., Волков А.В. с соавт. Роль иммунных механизмов и оральной микрофлоры в патогенезе периимплантитов. Бюллетень Оренбургского научного центра УрО РАН. 2019; (3): 9. (Labis V.V., Bazikyan E.A., Volkov A.V. et al. Role of immune mechanisms in oral microflora in the pathogenesis of periimplantitis. Byulleten’ Orenburgskogo nauchnogo tsentra Ural’skogo otdeleniya Rossiyskoy akademii nauk = Bulletin of the Orenburg Scientific Center of the Ural Branch of the Russian Academy of Sciences. 2019; (3): 9 (In Russ.)). EDN: IBZOCU.


4. Avila E.D., Oirschot B.A., Beucken J.P. Biomaterial-based possibilities for managing peri-implantitis. J Periodontal Res. 2020; 55(2): 165–73.


https://doi.org/10.1111/jre.12707. PMID: 31638267. PMCID: PMC7154698.


5. French D., Grandin H.M., Ofec R. Retrospective cohort study of 4,591 dental implants: analysis of risk indicators for bone loss and prevalence of periimplant mucositis and periimplantitis. J Periodontol. 2019; 90(7): 691–700.


https://doi.org/10.1002/JPER.18-0236. PMID: 30644101. PMCID: PMC6849729.


6. Camacho-Alonso F., Salinas J., Sanchez-Siles M. et al. Synergistic antimicrobial effect of photodynamic therapy and chitosan on the titanium-adherent biofilms of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa: An in vitro study. J Periodontol. 2022; 93(6): e104–15.


https://doi.org/10.1002/JPER.21-0306. PMID: 34541685.


7. Carvalho E.B.S., Romandini M., Sadilina S. et al. Microbiota associated with peri-implantitis – A systematic review with meta-analyses. Clin Oral Implants Res. 2023; 34(11): 1176–87.


https://doi.org/10.1111/clr.14153. PMID: 37523470.


8. Labis V., Bazikyan E., Zhigalina O. et al. Assessment of dental implant surface stability at the nanoscale level. Dent Mater. 2022; 38(6): 924–34.


https://doi.org/10.1016/j.dental.2022.03.003. PMID: 35289284.


9. Базикян Э.А., Лабис В.В., Козлов И.Г. с соавт. Патент № 2611013 С1 Способ персонифицированного подбора дентального имплантата на основе сплавов оксида титана: № 2015152570: заявлен 09.12.2015: опубликован 17.02.2017. (Bazikyan E.A., Labis V.V., Kozlov I.G. et al. Patent No. 2611013 C1 Method for personalized selection of a dental implant based on titanium oxide alloys: No. 2015152570: declared 12/09/2015: published 02/17/2017 (In Russ.)).


10. Лабис В.В., Базикян Э.А., Козлов И.Г. с соавт. Микробиологические и иммунологические аспекты взаимодействия Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli с наноразмерными металлическими частицами, полученными с поверхности дентальных имплантатов. Российский иммунологический журнал. 2017; 11(2): 166–169. (Labis V.V., Bazikyan E.A., Kozlov I.G. et al. Microbiological and immunological aspects of the interaction of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli with nanoscale metal particles, recieved from the surface of dental implants. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2017; 11(2): 166–169 (In Russ.)). EDN: ZCSCLL.


11. Бузмаков А.В., Асадчиков В.Е., Золотов Д.А. с соавт. Лабораторные микротомографы: конструкция и алгоритмы обработки данных. Кристаллография. 2018; 63(6): 1007–1111. (Buzmakov A.V., Asadchikov V.E., Zolotov D.A. et al. Laboratory microtomographs: Design and data processing algorithms. Crystallography Reports. 2018; 63(6): 1007–1111 (In Russ.)).


https://doi.org/10.1134/S0023476118060073. EDN: YMFSMH.


12. Румянцев П.О., Козлов И.Г., Колпакова Е.А. с соавт. IGG4-ассоциированные заболевания в эндокринологии. Проблемы эндокринологии. 2020; 66(2): 24–32. (Rumyantsev P.O., Kozlov I.G., Kolpakova E.A. et al. IGG4-related diseases in endocrinology. Problemy endokrinologii = Problems of Endocrinology. 2020; 66(2): 24–32 (In Russ.)).


https://doi.org/10.14341/probl12285. EDN: XSAAEV.


13. Hirai T., Yoshioka Y., Izumi N. et al. Metal nanoparticles in the presence of lipopolysaccharides trigger the onset of metal allergy in mice. Nat Nanotechnol. 2016; 11(9): 808–16.


https://doi.org/10.1038/nnano.2016.88. PMID: 27240418.


About the Autors


Varvara V. Labis, MD, PhD (Medicine), associate professor of the Department of propaedeutics of surgical dentistry, Russian University of Medicine of the Ministry of Healthcare of Russia. Address: 127473, Moscow, 20/1 Delegatskaya St.
E-mail: varvara2001@mail.ru
ORCID: https://orcid.org/0000-0001-7632-3234
Ernest A. Bazikyan, MD, Dr. Sci. (Medicine), head of the Department of propaedeutics of surgical dentistry, professor, dean of highly qualified personnel training, Russian University of Medicine of the Ministry of Healthcare of Russia, Honored Doctor of the Russian Federation. Address: 127473, Moscow, 20/1 Delegatskaya St.
E-mail: prof.bazikian@gmail.com
ORCID: https://orcid.org/0000-0002-9184-3737
Svetlana V. Sizova, MD, PhD (Chemistry), researcher at the Department of molecular biophysics, Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of RAS. Address: 117997, Moscow, 16/10 Miklouho-Maklaya St.
E-mail: sv.sizova@gmail.com
ORCID: https://orcid.org/0000-0003-0846-4670
Sergey V. Khaidukov, MD, Dr. Sci. (Biology), senior researcher at the Department of carbohydrates, Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of RAS. Address: 117997, Moscow, 16/10 Miklouho-Maklaya St.
E-mail: khsergey54@mail.ru
ORCID: https://orcid.org/0000-0003-1600-5335
Olga M. Zhigalina, MD, Dr. Sci. (Physics and Mathematics), leading researcher at National Research Center “Kurchatov Institute”. Address: 123182, Moscow, 1 Akademika Kurchatova Sq.
E-mail: zhigal@crys.ras.ru
ORCID: https://orcid.org/0000-0003-4721-4105
Dmitrii N. Khmelenin, MD, PhD (Physics and Mathematics), researcher at National Research Center “Kurchatov Institute”. Address: 123182, Moscow, 1 Akademika Kurchatova Sq.
Email: xorrunn@gmail.com
ORCID: https://orcid.org/0000-0003-0894-5087
Irina G. Dyachkova, MD, PhD (Physics and Mathematics), senior researcher at National Research Center “Kurchatov Institute”. Address: 123182, Moscow, 1 Akademika Kurchatova Sq.
E-mail: dyachkova.i@crys.ras.ru
ORCID: https://orcid.org/0000-0001-7615-6878
Denis A. Zolotov, MD, PhD (Physics and Mathematics), senior researcher at National Research Center “Kurchatov Institute”. Address: 123182, Moscow, 1 Akademika Kurchatova Sq.
E-mail: zolotovden@crys.ras.ru
ORCID: https://orcid.org/0000-0003-3701-9517
Victor E. Asadchikov, MD, Dr. Sci. (Physics and Mathematics), chief researcher at National Research Center “Kurchatov Institute”. Address: 123182, Moscow, 1 Akademika Kurchatova Sq.
E-mail: asad@crys.ras.ru
ORCID: https://orcid.org/0000-0003-3602-7582
Maria O. Isakina, 5th year student of N.F. Filatov Clinical Institute of Child Health of I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 19/1 Bol’shaya Pirogovskaya St.
E-mail: mery.isakina8@mail.ru
ORCID: https://orcid.org/0009-0008-3764-5941
Gelia N. Gildeeva, MD, Dr. Sci. (Medicine), professor, head of the Department of organization and management in the field of drug circulation, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 127018, Moscow, 1/17 Skladochnaya St.
E-mail: gildeeva_g_n@staff.sechenov.ru
ORCID: https://orcid.org/0000-0002-2537-2850
Ivan G. Kozlov, MD, Dr. Sci. (Medicine), professor, professor of the Department of organization and management in the field of drug circulation, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 127018, Moscow, 1/17 Skladochnaya St.
E-mail: immunopharmacology@yandex.ru
ORCID: https://orcid.org/0000-0002-9694-3234


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