Skip to main content

Advertisement

SpringerLink
Log in

Transforaminal and systemic diffusion of an active agent from a zinc oxide eugenol-based endodontic sealer containing hydrocortisone—in an in vivo model

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

This study aimed to quantify in vivo the release of hydrocortisone acetate (HCA) contained in a zinc oxide eugenol-based endodontic sealer, in various tissues.

Materials and methods

Roots of human teeth, shaped with One Shape single file and sealed with Endomethasone N, previously radiolabelled with tritium (3H-HCA), were implanted in the back of 24 mice. Mice were sacrificed at 2, 8, 24, and 48 h to evaluate and quantify the amount of radioactivity in subcutaneous tissues surrounding the apex (periapical-like) of the implanted teeth, blood, spleen, kidneys, liver, and urine.

Results

Radioactivity was released from the apex of the tooth into the periapical-like tissues with a peak measured at 2 h post-implantation (2.25% of the initial radioactivity/g). This quantity decreased significantly over time between 2 h and each time points. Radioactivity was still measured up to 48 h in the periapical-like tissues (0.42% of the initial radioactivity). The same pattern of kinetic was observed for all organs. The total quantity of radioactivity significantly decreased over time from 4.36% measured 2 h post-implantation to 0.74% at 48 h. Finally, about 10% of the initial radioactivity from Endomethasone N used to fill the root canal was retrieved after 48 h in the urine.

Conclusions

This study demonstrated that radioactive-HCA from Endomethasone N can diffuse through the apex of the root canal and follow a classical pharmacokinetics.

Clinical relevance

This mouse model shows that radioactive-HCA can diffuse through the apex and do not accumulate in periapical-like tissues and organs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. European Society of Endodontology (2006) Quality guidelines for endodontic treatment. Consensus report of the European Society of Endodontology. Int Endod J 39:921–930

    Article  Google Scholar 

  2. Arias A, De la Macorra JC, Hidalgo JJ, Azabal M (2003) Predictive models of pain following root canal treatment: a prospective clinical study. Int Endod J 46(8):784–793

    Article  Google Scholar 

  3. Ng YL, Glennon JP, Setchell DJ, Gulabivala K (2004) Prevalence of and factors affecting post-obturation pain in patients undergoing root canal treatment. Int Endod J 37(6):381–391

    Article  Google Scholar 

  4. European Medicines Agency (2011) Assessment report: hydrocortisone

  5. Lewis JG, Bagley CJ, Elder PA, Bachmann AW, Torpy DJ (2005) Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin. Clin Chim Acta 359(1–2):189–194

    Article  Google Scholar 

  6. Murphy D, West HF (1965) Hydrocortisone metabolism. Lancet 285:912–913

    Article  Google Scholar 

  7. Staquet MJ, Durand SH, Colomb E, Roméas A, Vincent C, Bleicher F, Lebecque S, Farges JC (2008) Different roles of odontoblasts and fibroblasts in immunity. J Dent Res 87(3):256–261

    Article  Google Scholar 

  8. Kokkas A, Goulas A, Stavrianos C, Anogianakis G (2011) The role of cytokines in pulp inflammation. J Biol Regul Homeost Agents 25(3):303–311

    PubMed  Google Scholar 

  9. Zanini M, Meyer E, Simon S (2017) Pulp inflammation diagnosis from clinical to inflammatory mediators: a systematic review. J Endod 43(7):1033–1051

    Article  Google Scholar 

  10. Coutaux A, Adam F, Willer JC, Le Bars D (2005) Hyperalgesia and allodynia: peripheral mechanisms. Joint Bone Spine 72(5):359–371

    Article  Google Scholar 

  11. Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nör JE (2008) Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 34(8):962–969

    Article  Google Scholar 

  12. Rosa V, Zhang Z, Grande RH, Nör JE (2013) Dental pulp tissue engineering in full-length human root canals. J Dent Res 92(11):970–975

    Article  Google Scholar 

  13. Fachin EV, Scarparo RK, Pezzi AP, Luisi SB, Sant'ana FM (2009) Effect of betamethasone on the pulp after topical application to the dentin of rat teeth: vascular aspects of the inflammation. J Appl Oral Sci 17:335–339

    Article  Google Scholar 

  14. Nobuhara WK, Carnes DL, Gilles JA (1993) Anti-inflammatory effects of dexamethasone on periapical tissues following endodontic overinstrumentation. J Endod 19(10):501–507

    Article  Google Scholar 

  15. Smith RG, Patterson SS, El-Kafrawy AH (1976) Histologic study of the effects of hydrocortisone on the apical periodontium of dogs. J Endod 2(12):376–380

    Article  Google Scholar 

  16. Jeanneau C, Giraud T, Milan JL, About I (2019) Investigating unset endodontic sealers’ eugenol and hydrocortisone roles in modulating the initial steps of inflammation. Clin Oral Investig 24:639–647. https://doi.org/10.1007/s00784-019-02957-2

    Article  PubMed  Google Scholar 

  17. Mehrvarzfar P, Shababi B, Sayyad R, Fallahdoost A, Kheradpir K (2008) Effect of supraperiosteal injection of dexamethasone on postoperative pain. Aust Endod J 34(1):25–29

    Article  Google Scholar 

  18. Kaufman E, Heling I, Rotstein I, Friedman S, Sion A, Moz C, Stabholtz A (1994) Intraligamentary injection of slow-release methylprednisolone for the prevention of pain after endodontic treatment. Oral Surg Oral Med Oral Pathol 77(6):651–654

    Article  Google Scholar 

  19. Copray JC, Mantingh I, Brouwer N, Biber K, Küst BM, Liem RS, Huitinga I, Tilders FJ, Van Dam AM, Boddeke HW (2001) Expression of interleukin-1 beta in rat dorsal root ganglia. J Neuroimmunol 118(2):203–211

    Article  Google Scholar 

  20. Schäfers M, Sorkin L (2008) Effect of cytokines on neuronal excitability. Neurosci Lett 437(3):188–193

    Article  Google Scholar 

  21. Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461

    Article  Google Scholar 

  22. Marshall JG, Liesinger AW (1993) Factors associated with endodontic posttreatment pain. J Endod 19(11):573–575

    Article  Google Scholar 

  23. Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, Shi S (2010) Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 16(2):605–615

    Article  Google Scholar 

  24. Syed-Picard FN, Ray HL Jr, Kumta PN, Sfeir C (2014) Scaffoldless tissue-engineered dental pulp cell constructs for endodontic therapy. J Dent Res 93(3):250–255

    Article  Google Scholar 

  25. Batista RFC, Hidalgo MM, Hernandes L, Consolaro A, Velloso TRG, Cuman RKN, Caparroz-Assef SM, Bersani-Amado CA (2007) Microscopic analysis of subcutaneous reactions to endodontic sealer implants in rats. J Biomed Mater Res A 81:171–177

    Article  Google Scholar 

  26. Albuquerque MT, Valera MC, Nakashima M, Nör JE, Bottino MC (2014) Tissue-engineering-based strategies for regenerative endodontics. J Dent Res 93(12):1222–1231

    Article  Google Scholar 

  27. Guarnieri M, Tyler BM, Detolla L, Zhao M, Kobrin B (2014) Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs. Pharm Bioallied Sci 6(1):38–42

    Article  Google Scholar 

  28. Modulevsky DJ, Cuerrier CM, Pelling AE (2016) Biocompatibility of subcutaneously implanted plant-derived cellulose biomaterials. PLoS One Jun 21:11(6)

    Google Scholar 

  29. Neethling WM, Glancy R, Hodge AJ (2010) Mitigation of calcification and cytotoxicity of a glutaraldehyde-preserved bovine pericardial matrix: improved biocompatibility after extended implantation in the subcutaneous rat model. J Heart Valve Dis 19(6):778–785

    PubMed  Google Scholar 

  30. Sasaki T, Watanabe C (1995) Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 16:9e15

    Article  Google Scholar 

  31. Balto K, Müller R, Carrington DC, Dobeck J, Stashenko P (2000) Quantification of periapical bone destruction in mice by micro-computed tomography. J Dent Res 79(1):35–40

    Article  Google Scholar 

  32. Pashley EL, Myers DR, Pashley DH, Whitford GM (1980) Systemic distribution of 14C-formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 59(3):602–608

    Article  Google Scholar 

  33. Hata GI, Nishikawa I, Kawazoe S, Toda T (1989) Systemic distribution of 14C-labeled formaldehyde applied in the root canal following pulpectomy. J Endod 15(11):539–543

    Article  Google Scholar 

  34. Krauser JA (2013) A perspective on tritium versus carbon-14 : Ensuring optimal label selection in pharmaceutical research and development. J Label Compd 56(9–10):441–446

    Article  Google Scholar 

  35. Badole GP, Warhadpande MM, Meshram GK, Bahadure RN, Tawani SG, Tawani G, Badole SG (2013) A comparative evaluation of cytotoxicity of root canal sealers: an in vitro study. Restor Dent Endod 38(4):204–209

    Article  Google Scholar 

  36. Abbott PV, Hume WR, Heithersay GS (1989) The release and diffusion through human coronal dentine in vitro of triamcinolone and demeclocycline from Ledermix® paste. Dent Traumatol 5:92–97

    Article  Google Scholar 

  37. Louwakul P, Lertchirakarn V (2012) Incorporation of anti-inflammatory agent into calcium hydroxide pulp capping material. An in vitro study of physical and mechanical properties. Dent Mater J 31:32–39

    Article  Google Scholar 

  38. Hechter O, Franck E, Caspi E, Franck H (1957) Corticosteroid metabolism in liver: in vivo metabolism of cortisone and cortisol by dog liver. Endocrinology 60(6):705–710

    Article  Google Scholar 

  39. Suzuki P, Souza V, Holland R, Gomes-Filho JE, Murata SS, Dezan Junior E, Passos TR (2011) Tissue reaction to Endomethasone sealer in root canal fillings short of or beyond the apical foramen. J Appl Oral Sci 19(5):511–516

    Article  Google Scholar 

Download references

Acknowledgments

Medical writing assistance was provided by Valerie Patin for Euraxi Pharma (Joué-les-Tours, France).

Funding

This study was funded by Septodont SAS (Saint-Maur-des-Fossés, Val-de-Marne, France).

Author information

Authors and Affiliations

  1. University of Nantes, UFR Odontologie & CHU Nantes, PHU 4 OTONN, 44042, Nantes, France

    Davy Aubeux & Fabienne Pérez

  2. Septodont SAS, 105 Avenue Beaurepaire, 94100, Saint-Maur-des-Fossés, France

    Anne Valot-Salengro & Arnaud Malet

  3. Chelatec SAS, 1 rue Arronax, 44800, St Herblain, France

    Gaelle Gautier

Authors
  1. Davy Aubeux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Valot-Salengro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaelle Gautier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arnaud Malet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabienne Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabienne Pérez.

Ethics declarations

Conflict of interest

Anne Valot-Salengro and Arnaud Malet are employees of Septodont, which sponsored the study.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

For this type of study, formal consent is not required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aubeux, D., Valot-Salengro, A., Gautier, G. et al. Transforaminal and systemic diffusion of an active agent from a zinc oxide eugenol-based endodontic sealer containing hydrocortisone—in an in vivo model. Clin Oral Invest 24, 4395–4402 (2020). https://doi.org/10.1007/s00784-020-03305-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-020-03305-5

Keywords

Search

Navigation