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Presence of Toxic Heavy Metals in Platelet-Rich Fibrin: a Pilot Study

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Abstract

Platelet-rich fibrin (PRF) is widely used blood-derived biomaterial which is directly applied to the surgical wounds. Depending on its autologous origin, PRF is thought as a safe material. However, it is not known to what extent the blood-derived toxins can be found in the PRF by considering the systemic exposure rates of the individuals to the toxins. The aim of this pilot study was to test the hypothesis whether PRF contains any blood-origin heavy metals (HMs) and smoking increases their concentrations as an environmental HM source. PRF samples were obtained from systemically healthy 30 non-smoker and 30 smoker volunteers. All liquid and dry fibrin parts of the PRF samples were analyzed in terms of 15 toxic elements using inductively coupled plasma mass spectrometry. All analyzed HMs were detected in all investigated PRF samples within various concentrations in both groups. In addition, significantly high levels of cadmium, arsenic, lead, manganese, nickel, chromium, and vanadium were detected in dry fibrin matrices of PRF samples of smokers comparing with non-smokers (p < 0.05). Only cadmium was at significantly high levels in the liquid part of PRF samples of smokers (p < 0.05). This is the first study evaluating toxic ingredients of PRF. The results revealed that PRF contains various toxic HMs. Additionally, systemic exposure to environmental HM sources such as smoking may significantly increase HM concentrations in PRF. Further studies are required to investigate the transmission potentials of HMs to the applied tissues and biological importance of PRF-origin HMs.

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References

  1. Bielecki T, Dohan Ehrenfest DM (2012) Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF): surgical adjuvants, preparations for in situ regenerative medicine and tools for tissue engineering. Curr Pharm Biotechnol 13(7):1121–1130

    Article  CAS  Google Scholar 

  2. Miron RJ, Zucchelli G, Pikos MA, Salama M, Lee S, Guillemette V, Fujioka-Kobayashi M, Bishara M, Zhang Y, Wang HL, Chandad F, Nacopoulos C, Simonpieri A, Aalam AA, Felice P, Sammartino G, Ghanaati S, Hernandez MA, Choukroun J (2017) Use of platelet-rich fibrin in regenerative dentistry: a systematic review. Clin Oral Investig 21(6):1913–1927

    Article  Google Scholar 

  3. Simonpieri A, del Corso M, Sammartino G, Dohan Ehrenfest DM (2009) The relevance of Choukroun’s platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part I: a new grafting protocol. Implant Dent 18(2):102–111

    Article  Google Scholar 

  4. Dohan DM, Del Corso M, Charrier JB (2007) Cytotoxicity analyses of Choukroun’s platelet rich fibrin (PRF) on a wide range of human cells: the answer to a commercial controversy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(5):587–593

    Article  Google Scholar 

  5. Oncu E, Kaymaz E (2017) Assessment of the effectiveness of platelet rich fibrin in the treatment of Schneiderian membrane perforation. Clin Implant Dent Relat Res 19(6):1009–1014

    Article  Google Scholar 

  6. Neirynck N, Glorieux G, Schepers E, Pletinck A, Dhondt A, Vanholder R (2013) Review of protein-bound toxins, possibility for blood purification therapy. Blood Purif 35(Suppl 1):45–50

    Article  CAS  Google Scholar 

  7. Ewers U, Krause C, Schulz C, Wilhelm M (1999) Reference values and human biological monitoring values for environmental toxins. Report on the work and recommendations of the Commission on Human Biological Monitoring of the German Federal Environmental Agency. Int Arch Occup Environ Health 72(4):255–260

    Article  CAS  Google Scholar 

  8. Singh R, Gautam N, Mishra A, Gupta R (2011) Heavy metals and living systems: an overview. Indian J Pharm 43(3):246–253

    Article  CAS  Google Scholar 

  9. Jarup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182

    Article  Google Scholar 

  10. Panhwar AH, Kazi TG, Afridi HI, Arain SA, Arain MS, Brahaman KD, Naeemullah, Arain SS (2016) Correlation of cadmium and aluminum in blood samples of kidney disorder patients with drinking water and tobacco smoking: related health risk. Environ Geochem Health 38(1):265–274

    Article  CAS  Google Scholar 

  11. Gil F, Pla A (2001) Biomarkers as biological indicators of xenobiotic exposure. J Appl Toxicol 21(4):245–255

    Article  CAS  Google Scholar 

  12. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7(2):60–72

    Article  Google Scholar 

  13. Bánfalvi G (2011) Cellular effects of heavy metals. Springer, Dordrecht xiv, 348 p

    Book  Google Scholar 

  14. Cobanoglu U, Demir H, Sayir F, Duran M, Mergan D (2010) Some mineral, trace element and heavy metal concentrations in lung cancer. Asian Pac J Cancer Prev 11(5):1383–1388

    PubMed  Google Scholar 

  15. McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98(12):869–873

    Article  CAS  Google Scholar 

  16. Sponder M, Fritzer-Szekeres M, Marculescu R, Mittlböck M, Uhl M, Köhler-Vallant B, Strametz-Juranek J (2014) Blood and urine levels of heavy metal pollutants in female and male patients with coronary artery disease. Vasc Health Risk Manag 10:311–317

    Article  Google Scholar 

  17. Nemery B (1990) Metal toxicity and the respiratory tract. Eur Respir J 3(2):202–219

    CAS  PubMed  Google Scholar 

  18. Lentini P, Zanoli L, Granata A, Signorelli SS, Castellino P, Dellaquila R (2017) Kidney and heavy metals—the role of environmental exposure (review). Mol Med Rep 15(5):3413–3419

    Article  CAS  Google Scholar 

  19. Monnet-Tschudi F, Zurich MG, Boschat C, Corbaz A, Honegger P (2006) Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases. Rev Environ Health 21(2):105–117

    Article  CAS  Google Scholar 

  20. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (2010) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol 95. Household use of solid fuels and high-temperature frying, pp 9–38

  21. Memon ZM, Yilmaz E, Shah AM, Sahin U, Kazi TG, Devrajani BR, Soylak M (2017) Trace elements in blood samples of smoker and nonsmoker active pulmonary tuberculosis patients from Jamshoro, Pakistan. Environ Sci Pollut Res Int 24(34):26513–26520

    Article  CAS  Google Scholar 

  22. Davydova S (2005) Heavy metals as toxicants in big cities. Microchem J 79(1–2):133–136

    Article  CAS  Google Scholar 

  23. Finch LE, Hillyer MM, Leopold MC (2015) Quantitative analysis of heavy metals in children’s toys and jewelry: a multi-instrument, multitechnique exercise in analytical chemistry and public health. J Chem Educ 92(5):849–854

    Article  CAS  Google Scholar 

  24. King KE, Darrah TH, Money E, Meentemeyer R, Maguire RL, Nye MD, Michener L, Murtha AP, Jirtle R, Murphy SK, Mendez MA, Robarge W, Vengosh A, Hoyo C (2015) Geographic clustering of elevated blood heavy metal levels in pregnant women. BMC Public Health 15:1035

    Article  Google Scholar 

  25. Wiwanitkit V (2008) Minor heavy metal: a review on occupational and environmental intoxication. Indian J Occup Environ Med 12(3):116–121

    Article  Google Scholar 

  26. Ruggieri F, Alimonti A, Bocca B (2016) Full validation and accreditation of a method to support human biomonitoring studies for trace and ultra-trace elements. TrAC Trends Anal Chem 80:471–485

    Article  CAS  Google Scholar 

  27. Yaprak E, Yolcubal İ, Sinanoğlu A, Doğrul-Demiray A, Guzeldemir-Akcakanat E, Marakoğlu İ (2017) High levels of heavy metal accumulation in dental calculus of smokers: a pilot inductively coupled plasma mass spectrometry study. J Periodontal Res 52(1):83–88

    Article  CAS  Google Scholar 

  28. Joseph P (2009) Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol 238(3):272–279

    Article  CAS  Google Scholar 

  29. Choong G, Liu Y, Templeton DM (2014) Interplay of calcium and cadmium in mediating cadmium toxicity. Chem Biol Interact 211:54–65

    Article  CAS  Google Scholar 

  30. Ding W, Templeton DM (2000) Activation of parallel mitogen-activated protein kinase cascades and induction of c-fos by cadmium. Toxicol Appl Pharmacol 162(2):93–99

    Article  CAS  Google Scholar 

  31. Matsuoka M, Call KM (1995) Cadmium-induced expression of immediate early genes in LLC-PK1 cells. Kidney Int 48(2):383–389

    Article  CAS  Google Scholar 

  32. Casalino E, Sblano C, Landriscina C (1997) Enzyme activity alteration by cadmium administration to rats: the possibility of iron involvement in lipid peroxidation. Arch Biochem Biophys 346(2):171–179

    Article  CAS  Google Scholar 

  33. Dally H, Hartwig A (1997) Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells. Carcinogenesis 18(5):1021–1026

    Article  CAS  Google Scholar 

  34. Asmuss M, Mullenders LH, Eker A, Hartwig A (2000) Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. Carcinogenesis 21(11):2097–2104

    Article  CAS  Google Scholar 

  35. Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192(2–3):95–117

    Article  CAS  Google Scholar 

  36. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51(2):257–281

    Article  CAS  Google Scholar 

  37. Mass MJ, Tennant A, Roop BC, Cullen WR, Styblo M, Thomas DJ, Kligerman AD (2001) Methylated trivalent arsenic species are genotoxic. Chem Res Toxicol 14(4):355–361

    Article  CAS  Google Scholar 

  38. Lynn S, Yew FH, Chen KS, Jan KY (1997) Reactive oxygen species are involved in nickel inhibition of DNA repair. Environ Mol Mutagen 29(2):208–216

    Article  CAS  Google Scholar 

  39. Kim HS, Kim YJ, Seo YR (2015) An overview of carcinogenic heavy metal: molecular toxicity mechanism and prevention. J Cancer Prev 20(4):232–240

    Article  Google Scholar 

  40. Costa M, Yan Y, Zhao D, Salnikow K (2003) Molecular mechanisms of nickel carcinogenesis: gene silencing by nickel delivery to the nucleus and gene activation/inactivation by nickel-induced cell signaling. J Environ Monit 5(2):222–223

    Article  CAS  Google Scholar 

  41. Jenner GA, Longerich HP, Jackson SE, Fryer BJ (1990) ICP-MS—a powerful tool for high-precision trace-element analysis in earth sciences—evidence from analysis of selected USGS reference samples. Chem Geol 83(1–2):133–148

    Article  CAS  Google Scholar 

  42. Vanhoe H (1993) A review of the capabilities of ICP-MS for trace-element analysis in body-fluids and tissues. J Trace Elem Electrolytes Health Dis 7(3):131–139

    CAS  PubMed  Google Scholar 

  43. Yaprak E, Kasap M, Akpinar G, Islek EE, Sinanoglu A (2018) Abundant proteins in platelet-rich fibrin and their potential contribution to wound healing: an explorative proteomics study and review of the literature. J Dent Sci 13(4):386–395

    Article  Google Scholar 

  44. Sotogaku N, Endo K, Hirunuma R, Enomoto S, Ambe S, Ambe F (1999) Binding properties of various metals to blood components and serum proteins: a multitracer study. J Trace Elem Med Biol 13(1–2):1–6

    Article  CAS  Google Scholar 

  45. Mosesson MW (2005) Fibrinogen and fibrin structure and functions. J Thromb Haemost 3(8):1894–1904

    Article  CAS  Google Scholar 

  46. Weisel JW, Litvinov RI (2017) Fibrin formation, structure and properties. Subcell Biochem 82:405–456

    Article  CAS  Google Scholar 

  47. Steven FS, Griffin MM, Brown BS, Hulley TP (1982) Aggregation of fibrinogen molecules by metal-ions. Int J Biol Macromol 4(6):367–369

    Article  CAS  Google Scholar 

  48. Su CY, Kuo YP, Tseng YH, Su CH, Burnouf T (2009) In vitro release of growth factors from platelet-rich fibrin (PRF): a proposal to optimize the clinical applications of PRF. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108(1):56–61

    Article  Google Scholar 

  49. He L, Lin Y, Hu X, Zhang Y, Wu H (2009) A comparative study of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108(5):707–713

    Article  Google Scholar 

  50. Kang YH, Jeon SH, Park JY, Chung JH, Choung YH, Choung HW, Kim ES, Choung PH (2011) Platelet-rich fibrin is a bioscaffold and reservoir of growth factors for tissue regeneration. Tissue Eng A 17(3–4):349–359

    Article  CAS  Google Scholar 

  51. Lundquist R, Dziegiel MH, Agren MS (2008) Bioactivity and stability of endogenous fibrogenic factors in platelet-rich fibrin. Wound Repair Regen 16(3):356–363

    Article  Google Scholar 

  52. Eren G, Gürkan A, Atmaca H, Dönmez A, Atilla G (2016) Effect of centrifugation time on growth factor and MMP release of an experimental platelet-rich fibrin-type product. Platelets 27(5):427–432

    Article  CAS  Google Scholar 

  53. Dohan Ehrenfest DM, de Peppo GM, Doglioli P, Sammartino G (2009) Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors 27(1):63–69

    Article  CAS  Google Scholar 

  54. Talhout R, Schulz T, Florek E, van Benthem J, Wester P, Opperhuizen A (2011) Hazardous compounds in tobacco smoke. Int J Environ Res Public Health 8(2):613–628

    Article  Google Scholar 

  55. Jain RB (2016) Selected volatile organic compounds as biomarkers for exposure to tobacco smoke. Biomarkers 21(4):342–346

    Article  CAS  Google Scholar 

  56. Chang CM, Edwards SH, Arab A, del Valle-Pinero AY, Yang L, Hatsukami DK (2017) Biomarkers of tobacco exposure: summary of an FDA-sponsored public workshop. Cancer Epidemiol Biomark Prev 26(3):291–302

    Article  CAS  Google Scholar 

  57. Jung SY, Kim S, Lee K, Kim JY, Bae WK, Lee K, Han JS, Kim S (2015) Association between secondhand smoke exposure and blood lead and cadmium concentration in community dwelling women: the fifth Korea National Health and Nutrition Examination Survey (2010-2012). BMJ Open 5(7):e008218

    Article  Google Scholar 

  58. Li L, Guo L, Chen X, Xiang M, Yang F, Ren JC, Zhang GH (2018) Secondhand smoke is associated with heavy metal concentrations in children. Eur J Pediatr 177(2):257–264

    Article  CAS  Google Scholar 

  59. Wasowicz W, Gromadzinska J, Rydzynski K (2001) Blood concentration of essential trace elements and heavy metals in workers exposed to lead and cadmium. Int J Occup Med Environ Health 14(3):223–229

    CAS  PubMed  Google Scholar 

  60. Buchet JP, Roels H, Bernard A, Lauwerys R (1980) Assessment of renal function of workers exposed to inorganic lead, calcium or mercury vapor. J Occup Med 22(11):741–750

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank clinic nurses Selda Yiğit Nilhan and Serap Karagüz for their support during the venous blood collection.

Funding

The study was financially supported by a grant from Kocaeli University Scientific Research Projects Fund; Grant Number: 2016/031.

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Correspondence to Emre Yaprak.

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The study was approved by the Ethics Committee of Kocaeli University (KOU GOKAEK 2016/191). Informed consent was obtained from all participants.

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The authors declare that they have no conflicts of interest.

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Yaprak, E., Yolcubal, İ. Presence of Toxic Heavy Metals in Platelet-Rich Fibrin: a Pilot Study. Biol Trace Elem Res 191, 363–369 (2019). https://doi.org/10.1007/s12011-019-01695-6

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  • DOI: https://doi.org/10.1007/s12011-019-01695-6

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