Local and systemic oxidative stress in chronic suppurative otitis media

Introduction. According to the literature, oxidative stress is described as one of the main factors in the pathogenesis of chronic suppurative otitis media, supporting the inflammatory process at the local level. The transition of inflammatory mediators to the systemic level is associated with the risk of developing ear purulent-destructive complications. The study of the products of lipid peroxidation in comparison with morphological changes in the structures of the temporal bone will justify the tactics of the operation.

Aim. Comparison of the levels of lipid peroxidation products at the local and systemic levels in chronic suppurative otitis media, depending on the nature of pathomorphological changes in the structures of the temporal bone.

Materials and methods. A prospective study of 130 patients with chronic suppurative otitis media at the age of 20-62 years with a verified diagnosis of chronic suppurative otitis media, admitted for surgical treatment, was carried out. To study the indicators of oxidative stress at the systemic level, the blood serum of patients was used; at the local level, the bone biomaterial obtained from patients during the surgical treatment of chronic suppurative otitis media was used. The quantitative determination of the primary, secondary and final products of peroxidation was carried out in the groups of patients with separate registration of lipoperoxides in the heptane and isopropanol phases of the lipid extract by spectrophotometry.

Results and discussion. In the observation of patients with morphological signs of purulent destruction of the temporal bone, not only a local level of inflammation activity, but also a systemic level of an unfavorable outcome was revealed in two variants: osteoproliferation or osteonecrosis of the bone tissue of the temporal bone in chronic purulent otitis media with a constant threat to the patient's life due to intracranial purulent complications.

Conclusion. The appearance in low concentrations of lipid peroxidation products in serum in patients with chronic purulent otitis media substantiates the need for a behind-the-ear approach in reconstructive-sanitizing otosurgery even with minimal clinical manifestations and CT scan data, since at the preclinical level it confirms the osteonecrotic type of bone remodeling with the risk of delayed death.

1. Palchun V.T. (ed.). Otorhinolaryngology. Moscow: GEOTAR-Media; 2016. 1012 p. (In Russ.). Available at: https://www.rosmedlib.ru/book/ISBN9785970437469.html.

2. Dubinets I.D., Kurenkov E.L., Kofanov R.V. Influence of the nature of morphological changes in the mucous membrane of the middle ear on the course of reparative processes in the nontympanic membrane during reconstructive sanitizing surgery in patients with chronic otitis media. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2007;(5):11-14. (In Russ.) Available at: https://elibrary.ru/item.asp?id=9576230.

3. Chung J.H., Lee S.H., Woo S.Y., Kim S.W., Cho Y.S. Prevalence and associated factors of chronic suppurative otitis media: Data from the Korea National Health and Nutrition Examination Survey, 2009-2012. Laryngoscope. 2016;126(10):2351-2357. https://doi.org/10.1002/lary.25981.

4. Bae S.H., Kwak S.H., Nam G.S., Jung J. Meta-analysis of Delayed Facial Palsy Following Middle Ear Surgery. Otol Neurotol. 2019;40(8):1109-1115. https://doi.org/10.1097/MAO.0000000000002318.

5. Dubinets I.D., Korkmazov M.Yu., Korkmazov A.M., Smirnov А.А., Gorbunov A.V. Comparative analysis of the nature and dynamics of the surgical treatment of patients with chronic otitis media according to the otorhinolaryngological department of the city of Chelyabinsk. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2017;82(S5):64-65. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=32285725.

6. Garov E.V. Chronic purulent otitis media: terminology, diagnosis and treatment tactics. RMJ. 2011;19(6):390-393. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=20168619.

7. Kryukov A.I., Garov E.V. The classification of operations in chronic suppurative otitis media. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology. 2016;3(82):181-182. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=26139245.

8. Tarasov D.I., Fedorova O.K., Bykova V.P Middle ear diseases. Moscow: Medicine; 1988. 285 p. (In Russ.) Available at: https://search.rsl.ru/ru/record/01001440808.

9. Patyakina O.K., Kryukov A.I., Garov E.V. The classification of chronic suppurative otitis media. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology. 2016;3(82):207-208. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=26139264.

10. Dubinets I.D. Classification criteria for the primary diagnosis of chronic suppurative otitis media. Rossiiskii meditsinskii zhurnal = Medical Journal of the Russian Federation. 2020;26(6):431-438. (In Russ.) Available at: https://elibrary.ru/item.asp?id=45539924.

11. Orji F.T., Dike B.O. Observations on the current bacteriological profile of chronic suppurative otitis media in South eastern Nigeria. Ann Med Health Sci Res. 2015;5(2):124-128. Available at: https://pubmed.ncbi.nlm.nih.gov/25861532/.

12. Li M.G., Hotez P.J., Vrabec J.T., Donovan D.T. Is chronic suppurative otitis media a neglected tropical disease? PLoS Negl Trop Dis. 2015;9(3):e0003485. https://doi.org/10.1371/journal.pntd.0003761.

13. Kryukov A.I., Ivoylov A.Y., Garov E.V., Pakina V.R., Yanovskiy V.V. Effect of microbial flora on the course of chronic suppurative otitis media. Meditsinskiy sovet = Medical Council. 2014;(3):21-23. (In Russ.) Available at: https://www.med-sovet.pro/jour/article/view/521?locale=ru_RU.

14. Arvind N., Chand P., Vishrutha K.V. Microbiological profile of chronic suppurative otitis media. Int J Biomed Res. 2014;5(3):204-206. Available at: https://www.researchgate.net/publication/273503277_Microbiological_profile_of_Chronic_Suppurative_Otitis_Media.

15. Kryukov A.I., Luchikhin L.A., Magomedov M.M., Garov E.V., Sidorina N.G., Karneeva O.V. et al. Chronic suppurative otitis media: clinical guidelines. Moscow; St Petersburg; 2014. 33 p. Available at: http://glav-otolar.ru/assets/images/docs/clinical-recomendations/clinical-recomendations%202014/HGSO%202014.pdf.

16. Korkmazov M.Yu., Dubinets I.D., Lengina M.A., Solodovnik A.V. Local concentrations of secretory immunoglobulin A in patients with adenoiditis, rhinosinusitis and exacerbation of chronic suppurative otitis media against the background of the use of physical methods in complex therapy. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2021;24(2):297-304. (In Russ.) Available at: https://www.rusimmun.ru/jour/article/view/999.

17. Korkmazov A.M., Korkmazov M.Yu. Methods of correction of functional disorders of phagocytes and local manifestations of oxidative stress in the nasal cavity mucosa using ultrasonic cavitation. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2018;12(3):325-328. (In Russ.) https://doi.org/10.31857/S102872210002404-9.

18. Korkmazov A.M., Korkmazov M.Yu., Dubinets I.D. Influence of low-frequency ultrasonic cavitation on the motor activity of the function of the ciliated epithelium after intranasal surgical interventions. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2016;81(S5):29-31. (In Russ.) Available at: https://elibrary.ru/item.asp?id=27636504.

19. Shisheva A.K., Korkmazov M.Yu. Socio-economic aspects of optimization of hospital care for patients with pathology of the nose and paranasal sinuses in a large industrial city. Vestnik Yuzhno- Uralskogo gosudarstvennogo universiteta = Bulletin of the South Ural State University. 2011;26(243):62-66. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=16922028.

20. Gizinger O.A., Korkmazov A.M., Korkmazov M.Yu. The state of factors of antimicrobial protection of nasal secretions in patients operated on for curvature of the nasal septum in the early postoperative period. Rossiyskiy immu-nologicheskiy zhurnal = Russian Journal of Immunology. 2017;11(20):117-119.. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=29826620.

21. Dubinets I.D., Korkmazov M.Yu., Sinitsky A.I., Sychugov G.V., Tyukhay M.V. Variants of bone tissue modification in chronic otitis media according to light and electron microscopy. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2019;84(3):16-21. (In Russ.) https://doi.org/10.17116/otorino20198403116.

22. Dubinets I.D., Sinitskiy A.I., Korkmazov M.Yu., Chernykh E.I., Kukhtik S.Yu. Oxidative modification of proteins of the temporal bone tissue in chronic otitis media. Kazanskiy meditsinskiy zhurnal = Kazan Medical Journal. 2019;100(2):226-231. (In Russ.) https://doi.org/10.17816/KMJ2019-226.

23. Yeh C.F., Wu C.S., Huang C.Y., Tang C.H., Kuo T.Y., Tu T.Y. Chronic otitis media surgery and re-operation risk factor analysis: A nationwide retrospective cohort study of 18 895 patients. Acta Otolaryngol. 2016;136(3):259-265. https://doi.org/10.3109/00016489.2015.1115550.

24. Kotelnikov G.P. (ed.) Interdisciplinary Aspects of Osteology. Samara: Samara State Medical University; 1999. 180 p (In Russ.) Available at: http://lib.tvgmu.ru/OpacUnicode/index.php?url=/notices/index/IdNotice:7603/Source:default.

25. Jane B. Lian Epigenetic pathways regulating bone homeostasis. Bone. 2015;81:731-732. https://doi.org/10.1016/j.bone.2015.05.036.

26. Kamilov F.KH., Farshatova E.R., Enikeev D.A. Cellular-molecular mechanisms of bone tissue remodeling and its regulation. Fundamentalnye issle-dovaniya = Basic Research. 2014;(7-4):836-842. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=21952323.

27. Raustyte G., Caye-Thomasen P., Hermansson A., Andersen H., Thomsen J. Calcium deposition and expression of bone modelling markers in the tympanic membrane following acute otitis media. Int J Pediatr Otorhinolaryngol. 2006;70(3):529-539. https://doi.org/10.1016/j.ijporl.2005.07.022.

28. Korkmazov A.M., Dubinets I.D., Lengina M.A. Possibilities of topical antioxidant protection of operated cavities in practical otorhinolaryngology. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2017;82(S5):14-15. (In Russ.) Available at: https://elibrary.ru/item.asp?id=32285713.

29. Vinel P.K., Grobovoy S.I., Sinitskii A.I., Kolesnikov O.L. Modification of a spectrophotometric method for assessment of monoamine oxidase activity with 2,4-dinitrophenylhydrazine as a derivatizing reagent. Anal Biochem. 2021;629:114294. https://doi.org/10.1016/j.ab.2021.114294.

30. Sinitskii A.I., Kochkina O.T., Grobovoi S.I. Influence of 2-ethyl-6-methyl-3-hydroxypyridine on the functional state of rat liver mitochondria in vitro. Khimiko-farmatsevticheskiy zhurnal = Pharmaceutical Chemistry Journal. 2021;55(1):6-10. https://doi.org/10.30906/0023-1134-2021-55-1-8-12.

31. Korkmazov A.M., Korkmazov M.Yu. Methods for correcting functional disorders of phagocytes and local manifestations of oxidative stress in the nasal mucosa using ultrasonic cavitation. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2018;12(3):325-328. (In Russ.) https://doi.org/10.31857/S102872210002404-9.

32. Dubinina E.E. Oxygen metabolism products in the functional activity of cells (life and death, creation and destruction). Physiological, clinical and biochemical aspects. St Petersburg: Medical Press; 2006. 397 p. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=19495143.

33. Bayke E.V., Bayke E.E. Modern ideas about the pathogenesis of chronic suppurative otitis media. Zabaykalskiy meditsinskiy vestnik = Transbaikal Medical Bulletin. 2015;(1):161-167. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=23170895.

34. Testa D., Guerra G., Marcuccio G., Landolfo P.G., Motta G. Oxidative stress in chronic otitis media with effusion. Acta Otolaryngol. 2012;132(8):834-837. https://doi.org/10.3109/00016489.2012.663504.

35. Celik M., Koyuncu i. A comprehensive study of oxidative stress in patients with chronic otitis media. ENT Updates. 2020;10(1):238-243. https://doi.org/10.32448/entupdates.630369.

36. Aschner M., Nguyen T.T., Sinitskii A.I., Santamaria A., Bornhorst J., Ajsuvakova O.P. et al. Isolevuglandins (isoLGs) as toxic lipid peroxidation byproducts and their pathogenetic role in human diseases. Free Radic Biol Med. 2021;162:266-273. https://doi.org/10.1016/j.freeradbiomed.2020.10.024.

37. Abramov K.S., Davydova E.V., Osikov M.V., Ogneva O.I., Sinitskiy A.I. Dynamics of changes in indicators of free radical oxidation in an isolated fracture of the femur in conditions of systemic ozone therapy. Patologicheskaya fiziologiya i eksperimentalnaya terapiya = Pathological Physiology and Experimental Therapy. 2021;65(1):79-85. (In Russ.) https://doi.org/10.25557/0031-2991.2021.01.79-85.

38. Dubinets I.D., Korkmazov M.Yu., Sinitskiy A.I., Uchaev D.A., Angelovich M.S. Changes in the elemental composition of the temporal bone in patients with chronic suppurative otitis media. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2020;85(5):44-50. (In Russ.) https://doi.org/10.17116/otorino20208505144.

39. Dubinets I.D., Korkmazov M.Yu., Tyukhay M.V. The role of structural changes in bone tissue in the performance of various types of reconstructive and sanitizing interventions in chronic inflammation of ENT organs. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2016;(S5):15-16. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=27636491.

40. Korkmazov M.Yu., Kryukov A.I., Dubinets I.D., Tyukhai M.V., Uchaev D.A., Markelov A.V. Classification of structural changes in bone tissue in chronic purulent otitis media. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2019;84(1):12-17. (In Russ.) https://doi.org/10.17116/otorino20198401112.

41. Goldberg A.L. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426:895-899. https://doi.org/10.1038/nature02263.

42. Shigemi H., Egashira T., Kurono Y., Mogi G. Role of superoxide dismutase in otitis media with effusion. Ann Otol Rhinol Laryngol. 1998;107(4):327-331. https://doi.org/10.1177/000348949810700411.

43. Yariktas M., Doner F., Dogru H., Yasan H., Delibas N. The role of free oxygen radicals on the development of otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2004;68(7):889-894. https://doi.org/10.1016/j.ijporl.2004.02.002.

44. Atashi F., Modarressi A., Pepper M.S. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review. Stem Cells Developm. 2015;24(10):1150-1163. https://doi.org/10.1089/scd.2014.0484.

45. Shouhed D., Kha H.T., Richardson J.A., Amantea C.M., Hahn T.J., Parhami F. Osteogenic oxysterols inhibit the adverse effects of oxidative stress on osteogenic differentiation of marrow stromal cells. J Cell Biochem. 2005;95(6):1276-1283. https://doi.org/10.1002/jcb.20497.

46. Mody N., Parhami F., Sarafian T.A. Demer L.L. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radical Biol Med. 2001;31(4):509-519. https://doi.org/10.1016/s0891-5849(01)00610-4.

47. Basu S., Michaëlsson K., Olofsson H., Johansson S., Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001;288(1):275-279. https://doi.org/10.1006/bbrc.2001.5747.

48. Fomina M.A., Abalenikhina Yu.V. A method of complex assessment of the content of oxidative modification products of proteins in tissues and biological fluids. Ryazan: Ryazan State Medical University; 2014. 60 p. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=22950036.

49. Volchegorsky I.A., Nalimov A.G., Yarovinsky B.G., Lifshits R.I. Comparison of different approaches to the determination of lipid peroxidation products in heptane-isopropanol extracts of blood. Voprosy meditsinskoy khimii = Questions of Medicinal Chemistry. 1989;35(1):127-131. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=21854857.

50. Lvovskaya E.I., Volchegorskiy I.A., Shemyakov S.E., Lifshits R.I. Spectrophotometric determination of end products of lipid peroxidation. Voprosy meditsinskoy khimii = Questions of medicinal chemistry. 1991;37(4):92-93. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=21963251.

51. Fletcher R., Fletcher S., Vagner E. Clinical epidemiology. Evidence-Based Medicine Fundamentals. Problemy ehndokrinologii = Endocrinology Problems. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=41039711.