Khudan R. I., Kyryliv M. V., Bekus I. R., Korda M. M.

DENTISTRY

Scentific article

The progression of destructive event in periodontal tissues depends on many factors, including comorbid somatic pathologies. In Ukraine, the syndrome of hyperhomocysteinemia (HHcy) is found in 10% of healthy adults, 13-43% of patients with arterial hypertension and coronary heart disease and 55% of patients with ischemic strokes. Data on the relationship between HHcy and generalized periodontitis are limited and contradictory. Purpose of work: to establish the features of the cytokine profile of blood serum and periodontal homogenate of rats with lipopolysaccharide (LPS)-induced periodontitis combined with chronic HHcy. Object and methods. The study included 48 mature inbred white male rats, which were randomly divided into the following groups: control (n=12); animals with a model of periodontitis (n=12). For two weeks, the rats in this group were injected 40 μL (1 mg/mL) of E. coli LPS (manufactured by Sigma-Aldrich, USA) into gingival tissues every other day; rats with chronic thiolactone HHcy (n=12). Homocysteine thiolactone was administered intragastrically (100 mg/kg of body weight in 1 % solution of starch) once a day for 42 days; animals with a model of periodontitis combined with HHcy (n=12). The contents of TNF-α, IL-1β and IL-10 were studied by a solid-phase enzyme-linked immunosorbent assay using RayBio reagent kits manufactured by RayBiotech (USA) according to the manufacturer’s protocol on a Multiscan FC analyzer (Thermo Scietific, Finland). Results. It was found that LPS-induced periodontitis in rats is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1β) on the background of reduced anti-inflammatory cytokine (IL-10), both in periodontal homogenate and in blood serum. Chronic HHcy exacerbates cytokine imbalance in LPS-induced periodontitis, as indicated by the significant predominance of TNF-α contents in rats with LPS-induced periodontitis combined with HHcy vs. rats with LPS-induced periodontitis without comorbid pathology both in blood serum (by 48.00%) and in the periodontal homogenate (by 2.3 times). Conclusions. LPS-induced periodontitis in rats is accompanied by cytokine dysbalance, which plays an important role in the initiation and progression of periodontitis and the initiation of metabolic cascade reactions. Chronic HHcy exacerbates cytokine imbalance in LPS-induced periodontitis.

: periodontitis, hyperhomocysteinemia, interleukins, homocysteine.

1. Riznyk SS, Riznyk YuB. Tsytokinovyi status khvorykh na heneralizovanyi parodontyt na tli tsukrovoho diabetu II typu. Suchasna stomatolohiia 2020;4:22-25. [in Ukrainian].
2. Popovych IYu, Petrushanko TO. Mozhlyvosti likuvannia patsiientiv iz khronichnym heneralizovanym parodontytom. Visnyk stomatolohii. 2020;2(111):27-33. [in Ukrainian].
3. Suragimath G, Doshi D, Varma S, A. Zope S, SR A. Effect of non-surgical periodontal therapy on salivary and serum leptin levels in patients with generalized stage II grade B periodontitis. Journal of Stomatology. 2021;74(2):84-88.
4. Mashchenko IS, Hudar’ian OO, Kucherenko TO. Klinichni, imunolohichni ta metabolichni osoblyvosti zahostrenoho i shvydko prohresuiuchoho variantiv heneralizovanoho parodontyta. Suchasna stomatolohiia 2020;4:26-32. [in Ukrainian].
5. Kolenko YuH, Volovyk IA, Mialkivskyi KO. Vplyv zakhvoriuvan tkanyn parodonta na yakist zhyttia patsiientiv. Suchasna stomatolohiia. 2021;2:36-42. [in Ukrainian].
6. Shcherba VV, Krynytska IYa, Korda MM. Zminy tsytokinovoho profiliu v shchuriv z parodontytom na tli hiper- ta hipotyreozu. Medychna ta klinichna khimiia. 2019;21(2):36-43. [in Ukrainian].
7. Duvina M, Barbato L. Biochemical markers as predictors of bone remodelling in dental disorders: a narrative description of literature. Clin. Cases Miner. Bone Metab. 2012;9(2):100-106.
8. Naumova VN, Turkyna SV, Maslak EE. Vzaimosvyaz stomatologicheskikh i somaticheskikh zabolevaniy: obzor literatury. Volgogradskiy nauchno-meditsinskiy zhurnal. 2016;2:25-28. [in Russian].
9. Leonteva EYu, Bykovskaya TYu, Kyreev VV. Analiz komorbidnosti stomatologicheskoy i obshchesomaticheskoy patologii meditsinskikh rabotnikov. Sovremennyye problemy nauki i obrazovaniya. 2017;4:1. [in Russian].
10. Prodanchuk AI, Kiiun ID, Kroitor MO. Zakhvoriuvannia parodonta i somatychna patolohiia. Bukovynsʹkyy medychnyy visnyk. 2012;16(2):164- 168. [in Ukrainian].
11.  Yurchenko PO, Melnyk AV, Zaichko NV, Yoltukhivskyi MM. Osoblyvosti obminu homotsysteinu ta hidrohen sulfidu v tsentralnii nervovii systemi. Medychna khimiia. 2014;3(60):90-96. [in Ukrainian].
12. Nechyporuk VM, Zaichko NV, Melnyk AV, Ostreniuk RS, Korda MM. Vplyv khronichnoi hiperhomotsysteinemii na metabolizm sirkovmisnykh aminokyslot u nyrkakh shchuriv pry hiper- ta hipotyreozi. Visnyk naukovykh doslidzhen. 2019;1:97-102. [in Ukrainian].
13. Nekrut DO. Vplyv hiperhomotsysteinemii na formuvannia nealkoholnoi zhyrovoi khvoroby pechinky u shchuriv. Visnyk morfolohii 2016;1;.22:40-45. [in Ukrainian].
14. Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J. Intern. Med. 2021;2021:1-29. doi: 10.1111/ joim.13279.
15. Rehman T, Shabbir MA, Inam-Ur-Raheem M, Manzoor MF, Ahmad N, Liu ZW, et al. Cysteine and homocysteine as biomarker of various diseases. Food Sci. Nutr. 2020;8:4696-4707.
16. Cordaro M, Siracusa R, Fusco R, Cuzzocrea S, Di Paola R, Impellizzeri D. Involvements of hyperhomocysteinemia in neurological disorders. Metabolites. 2021;11:37.
17. Salvio G, Ciarloni A, Cutini M, Balercia G. Hyperhomocysteinemia: Focus on endothelial damage as a cause of erectile dysfunction. Int. J. Mol. Sci. 2021;22:418.
18. Mallapragada S, Kasana J, Agrawal P. Effect of Nonsurgical Periodontal Therapy on Serum Highly Sensitive Capsule Reactive Protein and Homocysteine Levels in Chronic Periodontitis: A Pilot Study. Contemp Clin Dent. 2017;8(2):279-285.
19. Penmetsa GS, Bhaskar RU, Mopidevi A. Analysis of plasma homocysteine levels in patients with chronic periodontitis before and after nonsurgical periodontal therapy using high-performance liquid chromatography. Contemp Clin Dent. 2020;11:266-273.
20. Botelho J, Machado V, Leira Y, Proença L, Mendes JJ. Periodontal Inflamed Surface Area Mediates the Link between Homocysteine and Blood Pressure. Biomolecules. 2021;11(6):875.
21. Navarro BG, Salas EJ, López JL, Sala XP. Is there a relationship between dental and/or periodontal pathology and values of C-reactive protein, homocysteine and lipoprotein (a) in patients with cardiovascular disease? A Case Control Study. Journal of Current Medical Research and Opinion. 2020;3(05):451-458.
22. Stanisic D, Jovanovic M, George AK, Homme RP, Tyagi N, Singh M, et al. Gut microbiota and the periodontal disease: role of hyperhomocysteinemia. Can J Physiol Pharmacol. 2021;99(1):9-17.
23. Krivosheyeva EM, Fefelova EV, Borodulina II, Sepp AV, Borodulina NV. Effektivnost adaptogenov pri eksperimentalnom parodontite na fone gipergomotsisteinemii. Byulleten VSNTS SO RAMN. 2010;3(73):221-225. [in Russian].
24. Moiseyeva EG. Metabolicheskiy gomeostaz i immunnaya reaktivnost organizma v dinamike vospaleniya v tkanyakh parodonta (eksperimentalnoye issledovaniye) [dysertatsiia]. Moskva: Rossiyskiy Universitet druzhby narodov; 2008. 45 s. [in Russian].
25. Stangl GI. Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats. Exp. Biol. Med. 2007;232(1):81-87.
26. Zinina EP, Tsarenko SV, Logunov DYu, Tukhvatulin AI, Babayants AV, Avramov AA. Rol provospalitelnykh i protivovospalitelnykh tsitokinov pri bakterialnoy pnevmonii. Obzor literatury. Vestnik intensivnoy terapii im. A.I. Saltanova. 2021;1:77-89. [in Russian].
27. Krynytska I, Marushchak M, Svan O, Akimova V, Mazur L, Habor H. The indices of endogenous intoxication in rats with carrageenan solution consumption. Georgian Medical News. 2018;(279):196-200.
28. Sabirova AI. Tsitokinovyy status u bolnykh generalizovannym parodontitom i metabolicheskim sindromom. Vestnik KRSU. 2016;16(7):102- 105. [in Russian].
29. Borysenko AV, Kolenko YUH, Linovytska LV, Nesin OF, Timokhina TO, Pechkovskyy KYE. Osoblyvosti mistsevoho imunitetu porozhnyny rota u khvorykh na heneralizovanyy parodontyt i suputni zahalni zakhvoryuvannya. Suchasna stomatolohiya. 2019;5:34-39. [in Ukrainian].
30. Al-Ghurabi BH, Shaker ZF, Al-Hassan AA. Clinical relevance of IL-1Β/IL-10 and TNF-Α/IL-10 ratio in chronic periodontitis patients. Int J Recent Sci Res. 2013;4(3):275-277.
31. Oh H, Hirano J, Takai H, Ogata Y. Effects of initial periodontal therapy on interleukin-1β level in gingival crevicular fluid and clinical periodontal parameters. Int J Oral Sci. 2015;57(2):67-71.
32. Ikezawa-Suzuki I, Shimada Y, Tai H, Komatsu Y, Tanaka A, Yoshie H. Effects of treatment on soluble tumour necrosis factor receptor type 1 and 2 in chronic periodontitis. J Clin Periodontol. 2008;35(11):961-968.
33. Elkhouli A. The efficacy of host response modulation therapy (omega-3 plus low-dose aspirin) as an adjunctive treatment of chronic periodontitis (Clinical and biochemical study). J Periodontal Res. 2011;46(2):261-268.
34. Dutzan N, Gamonal J, Silva A, Sanz M, Vernal R. Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL)-17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis. J Clin Periodontol. 2009;36(5):396-403.
35. Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019;11:30.
36. Shcherba V, Krynytska I, Marushchak M, Korda M. Does thyroid dysfunction infuence inflammatory mediators in experimental periodontitis? Endocrine regulations. 2021;55(3):101-111.
37. Shmidt DV. Tsitokiny desnevoy zhidkosti; ikh rol v patogeneze i kontrole lecheniya khronicheskogo parodontita [dysertatsiia]. Perm: Institut ekologii i genetiki mikroorganizmov UrO RAN; 2009. 21 s. [in Russian].
38. Lazzerini PE, Selvi E, Lorenzini S, Capecchi PL, Ghittoni R, Bisogno S, et al. Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthritis patients. Clin Exp Rheumatol. 2006;24(4):387-393.
39. Wang XJ, Tian DC, Wang FW, Zhang MH, Fan CD, Chen W, et al. Astaxanthin inhibits homocysteine-induced endothelial cell dysfunction via the regulation of the reactive oxygen species-dependent VEGF-VEGFR2-FAK signaling pathway. Mol Med Rep. 2019;19(6):4753- 4760.
40. Myslivets MG, Naumov AV, Paramonova NS. Rol’ gomotsisteina v razvitii yuvenilnogo revmatoidnogo artrita. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2017;2:144-148. [in Russian].

«Bulletin of problems biology and medicine» Issue 3 (161), 2021 year, 337-342 pages, index UDK 616.153.478.6-06:616.314.17-008.1-097:577.114.4]-092.9

10.29254/2077-4214-2021-3-161-337-342