Amalgam Dolgulu Hastalarda ve Diş Hekimlerinde Plazma MikroRNA'lar ile Serum Civa Düzeyleri Arasındaki İlişki

Abstract

Amaç: Bu çalışmanın amacı, amalgam dolgusu olan hastalarda ve diş hekimlerinde serum civa ve nörolojik hastalıklarla ilişkili bazı plazma mikroRNA (miRNA) seviyeleri arasındaki ilişkiyi araştırmaktır. Gereç ve Yöntemler: Bu çalışmaya 30 amalgam dolgulu hasta, 30 diş hekimi ve 30 sağlıklı kontrol grubu dahil edildi. Dolaşımdaki plazma miRNA'lar (124-3p, 125-5p ve 127-3p), gerçek zamanlı kantitatif polimeraz zincir reaksiyonu analizi kullanılarak değerlendirildi. Serum civa seviyeleri, endüktif olarak eşleşmiş plazma-kütle spektrometresi kullanılarak ölçüldü. İstatistiksel analizler için ANOVA ve Tukey’in çoklu karşılaştırma testleri kullanıldı (α = .05). Bulgular: Gruplar arasında serum civa ve plazma miRNA seviyelerinde anlamlı bir fark bulundu. Hasta grubunda serum civa ile plazma miRNA 125-5p ve 127-3p seviyeleri arasında anlamlı pozitif korelasyonlar tespit edildi (sırasıyla r: 0.56 ve r: 0.39). Serum civa ve plazma miRNA-125-5p seviyeleri, diş hekimi grubunda pozitif bir korelasyon gösterdi (r: 0.37). Sonuç: Amalgam dolguya sahip olmak serum civa ve plazma miRNA düzeylerinde önemli bir artışa neden olmuştur. Pozitif bir korelasyonun varlığı, civa maruziyeti nedeniyle nörolojik hastalıklara duyarlılığın artabileceğini göstermektedir. Amalgam dolgu için alternatif restoratif materyaller tercih edilmeli ve amalgam dolgular, gerekli önlemler alınarak diğer restoratif materyaller ile değiştirilmelidir.

Keywords

• Dental amalgam
• civa
• restoratif materyal

The Relationship Between Plasma MicroRNAs and Serum Mercury Levels in Patients with Amalgam Filling and Dentists

Abstract

Background: The aim of this study was to investigate the relationship between serum mercury and some plasma microRNA (miRNA) levels associated with neurological diseases in patients with amalgam filling and dentists. Methods: This study included 30 patients with amalgam filling, 30 dentists, and 30 healthy individuals as the control group. Circulating plasma miRNAs (124-3p, 125-5p, and 127-3p) were evaluated using real-time quantitative polymerase chain reaction analysis. The serum mercury levels were measured using inductively coupled plasma-mass spectrometry. ANOVA and Tukey’s multiple comparison tests were used for statistical analyses (α =.05). Results: A significant difference in serum mercury and plasma miRNA levels was found between the groups. Significant positive correlations between serum mercury and plasma miRNA 125-5p and 127-3p levels were detected in the patient group (r: 0.56 and r: 0.39, respectively). Serum mercury and plasma miRNA-125-5p levels showed a positive correlation in the dentist group (r: 0.37). Conclusion: Having amalgam filling caused a significant increase in serum mercury and plasma miRNA levels. The presence of a positive correlation suggests that sensitivity to neurological diseases may increase because of mercury exposure. Alternative restorative materials should be preferred for amalgam filling and amalgam fillings should be replaced with other restorative materials under necessary preventions.

Keywords

• dental amalgam
• mercury
• restorative material

References

1. Referans 1. Chin G, Chong J, Kluczewska A, Lau A, Gorjy S. The environmental effects of dental amalgam. Aust Dent J 2000;45:246-9.
2. Referans 2. Counter SA, Buchanan LH. Mercury exposure in children: a review. Toxicol Appl Pharmacol 2004;198:209-30.
3. Referans 3. Berlin M, Zalups RK, Fowler BA. Mercury. In: Nordberg G, Fowler RA, Nordberg M, Friberg LT (eds). Handbook on the toxicology of metals. 3rd ed. Burlington: Academic Press, 2007.
4. Referans 4. Langan DC, Fan PL, Hoos AA. The use of mercury in dentistry: a critical review of the recent literature. J Am Dent Assoc 1987;115:867- 80.
5. Referans 5. Yip HK, Li DK, Yau DC. Dental amalgam and human health. Int Dent J 2003;53:464-8.
6. Referans 6. Godfrey ME, Wojcik DP, Krone CA. Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. J Alzheimers Dis 2003;5:189-95.
7. Referans 7. Langworth S, Bjorkman L, Elinder CG, JärupL, Savlin P. Multidisciplinary examination of patients with illness attributed to dental fillings. J Oral Rehabil 2002;29:705-13.
8. Referans 8. Hock C, Drasch G, Golombowski S, Müller-Spahn F, Willershausen-Zönnchen B, Schwarz P, et al. Increased blood mercury levels in patients with Alzheimer's Disease. J Neural Transm 1998;105:59-68.

9. Referans 9. Bjørklund G, Hilt B, Dadar M, Lindh U, Aaseth J. Neurotoxic effects of mercury exposure in dental personnel. Basic Clin Pharmacol Toxicol 2019;124:568-74.
10. Referans 10. Bilen J, Liu N, Bonini NM. A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins. Cell Cycle 2006;5:2835–8.
11. Referans 11. Johnson R, Noble W, Tartaglia GG, Buckley NJ. Neurodegeneration as an RNA disorder. Prog Neurobiol 2012;99:293–315.
12. Referans 12. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol 2002;12:735–9.
13. Referans 13. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of micro-RNAs during brain development. RNA 2003;9:1274–81.
14. Referans 14. Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, et al. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 2004;5:R68.
15. Referans 15. Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative premRNA splicing. Mol Cell 2007;27:435–48.
16. Referans 16. Le MT, Shyh-Chang N, Khaw SL, Chin L, Teh C, Tay J, et al. Conserved regulation of p53network dosage by microRNA-125b occurs through evolving miRNA-target genepairs. PLoS Genet 2011;7:e1002242.
17. Referans 17. Khudayberdiev SA, Zampa F, Rajman M, Schratt G. A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons. Front Mol Neurosci Epub ahead of print 17 Oct 2013. DOI: 10.3389/fnmol.2013.00043
18. Referans 18. Björkman L, Sjursen TT, Dalen K, Lygre GB, Berge TLL , Svahn J, et al. Long term changes in health complaints after removal of amalgam restorations. Acta Odontol Scand 2017;75:208-19.
19. Referans 19. Aydin N, Karaoglanoglu S, Yigit A, Keles MS, Kirpinar I, Seven N. Neuropsychological effects of low mercury exposure in dental staff in Erzurum, Turkey. Int Dent J 2003;53:85-91.
20. Referans 20. Erkekoğlu P, Kadıoğlu E. Mercury Poisoning And Treatment. Toxicol Bull 2013;37:6-9.
21. Referans 21. Heyer NJ, Echeverria D, Bittner AC, Farin FM, Garabedian CC, Woods JS. Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood. Toxicol Sci 2004;81:354–63.
22. Referans 22. Martin MD, Naleway C, Chou HN. Factors contributing to mercury exposure in dentists. J Am Dent Assoc 1995;126:1502–11.
23. Referans 23. Langworth S, Sallsten G, Barregard L, Cynkier I, Lind ML, Söderman E. Exposure to mercury vapor and impact on health in the dental profession in Sweden. J Dent Res 1997;76:1397-1404.
24. Referans 24. Dock L, Vahter M. Metal toxicology. In: Ballantyne B, Marrs TC and Syversen T (eds) General and applied toxicology. 2nd ed. London: Macmillan Reference Books, 1999.
25. Referans 25. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury—current exposures and clinical manifestations. N Engl J Med 2003;349:1731-7.
26. Referans 26. Abraham J, Svare C, Frank C. The effects of dental amalgam restorations on blood mercury levels. J Dent Res 1984;63:71-73.
27. Referans 27. Nilsson B, Nilsson B. Mercury in dental practice the working environment of dental personel and their exposure to mercury vapor. Swed Den J 1986;10:1-14.
28. Referans 28. Molin M, Bergman B, Marklund SL, Schütz A, Skerfving S. Mercury, selenium and glutathine peroxidase before and after amalgam renoval in man. Acta Odontal Scand 1990;48:189-202.
29. Referans 29. Neghab M, Choobineh A, Zadeh JH, Ghaderi E. Symptoms of Intoxication in Dentists Associated with Exposure to Low Levels of Mercury. Ind Health 2011;49:249-54.
30. Referans 30. Lindbohm ML, Ylöstalo P, Sallmén M, Henriks-Eckerman MJ, Nurminen T, Forss H, Taskinen H. Occupational exposure in dentistry and miscarriage. Occup Envirom Med 2007;64:127–33.
31. Referans 31. Pesch A, Wilhelm M, Rostek U, Schmitz N, Weishoff-Houben M, Ranft U, et al. Mercury concentrations in urine, scalp hair, and saliva in children from Germany. J Exposure Anal Environ Epidemiol 2002;12:252-8.
32. Referans 32. McGrother CW, Dugmore C, Phillips MJ, Raymond NT, Garrick P, Baird WO. Multiple sclerosis, dental caries and fillings: a case-control study. Br Dent J 1999;187:261-4.
33. Referans 33. DeRouen TA, Martin MD, Leroux BG, Townes BD, Woods JS, Leitão J, et al. Neurobehavioral effects of dental amalgam in children: a randomized clinical trial. JAMA 2006;295:1784-92.
34. Referans 34. Li N, Pan X, Zhang J, Ma A, Yang S, Ma J, et al. Plasma levels of mir-137 and mir-124 are associated with parkinson's disease but not with parkinson's disease with depression. Neurol Sci 2017;38:761-7.
35. Referans 35. Kapsimali M, Kloosterman WP, De Bruijn E, Rosa F, Plasterk RHA, Wilson SW. MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Biol 2007;8:R173.
36. Referans 36. Diaz NF, Cruz-Resendiz MS, Flores-Herrera H, García-López G, Molina-Hernández A. MicroRNAs in central nervous system development. Rev Neurosci 2014;25:675-86.
37. Referans 37. Kang Q, Xiang Y, Li D, Liang J, Zhang X, Zhou F, et al. Mir-124-3p attenuates hyperphosphorylation of tau protein-induced apoptosis via caveolin-1-pi3k/akt/gsk3beta pathway in n2a/app695swe cells. Oncotarget 2017;8:24314-26.
38. Referans 38. Smith P, Al Hashimi A, Girard J, Delay C, Hébert SS. In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. J Neurochem 2011;116:240-7.
39. Referans 39. Fang M, Wang J, Zhang X, Geng Y, Hu Z, Rudd JA, et al. The miR-124 regulates the expression of BACE1/beta-secretase correlated with cell death in Alzheimer’s disease. Toxicol Lett 2012;209:94–105.
40. Referans 40. Dong RF, Zhang B, Tai LW, Liu HM, Shi FK, Liu NN. The Neuroprotective Role of miR-124-3p in a 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease via theRegulation of ANAX5. J Cell Biochem 2018;119:269-77.
41. Referans 41. Barca-Mayo O, Tonelli DDP. Convergent microRNA actions coordinate neocortical development. Cell Mol Life Sci 2014;71:2975–95.
42. Referans 42. Chinta SJ, Andersen JK. Dopaminergic neurons. The Int J Biochemistry & Cell Biology 2005;37:942-6.
43. Referans 43. Le MT, Xie H, Zhou B, Chia PH, Rizk P, Um M, et al. MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol 2009;29:5290–305.
44. Referans 44. Roese-Koerner B, Stappert L, Koch P, Borghese L. Pluripotent stem cell-derived somatic stem cells as tool to study the role of microRNAs in early human neural development. Curr Mol Med 2013;13:707–22.
45. Referans 45. Boissart C, Nissan X, Giraud-Triboult K, Peschanski M, Benchoua A. miR-125 potentiates early neural specification of human embryonic stem cells. Development 2012;139:1247-57.
46. Referans 46. Piscopoa P, Grassob M, Puopoloa M, D'Acunto E, Talarico G, Crestini A, et al. Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia. J Alzheimers Dis 2018;65:455-64.
47. Referans 47. Ebrahimkhani S, Vafaee F, Young PE, Hur SSJ, Hawke S, Devenney E, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep 2017;7:14293.