Skip to main content
Erschienen in: Clinical Oral Investigations 12/2020

08.05.2020 | Original Article

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

verfasst von: Davy Aubeux, Anne Valot-Salengro, Gaelle Gautier, Arnaud Malet, Fabienne Pérez

Erschienen in: Clinical Oral Investigations | Ausgabe 12/2020

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat European Society of Endodontology (2006) Quality guidelines for endodontic treatment. Consensus report of the European Society of Endodontology. Int Endod J 39:921–930CrossRef European Society of Endodontology (2006) Quality guidelines for endodontic treatment. Consensus report of the European Society of Endodontology. Int Endod J 39:921–930CrossRef
2.
Zurück zum Zitat 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):784–793CrossRef 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):784–793CrossRef
3.
Zurück zum Zitat 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):381–391CrossRef 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):381–391CrossRef
4.
Zurück zum Zitat European Medicines Agency (2011) Assessment report: hydrocortisone European Medicines Agency (2011) Assessment report: hydrocortisone
5.
Zurück zum Zitat 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):189–194CrossRef 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):189–194CrossRef
6.
Zurück zum Zitat Murphy D, West HF (1965) Hydrocortisone metabolism. Lancet 285:912–913CrossRef Murphy D, West HF (1965) Hydrocortisone metabolism. Lancet 285:912–913CrossRef
7.
Zurück zum Zitat 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):256–261CrossRef 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):256–261CrossRef
8.
Zurück zum Zitat Kokkas A, Goulas A, Stavrianos C, Anogianakis G (2011) The role of cytokines in pulp inflammation. J Biol Regul Homeost Agents 25(3):303–311PubMed Kokkas A, Goulas A, Stavrianos C, Anogianakis G (2011) The role of cytokines in pulp inflammation. J Biol Regul Homeost Agents 25(3):303–311PubMed
9.
Zurück zum Zitat Zanini M, Meyer E, Simon S (2017) Pulp inflammation diagnosis from clinical to inflammatory mediators: a systematic review. J Endod 43(7):1033–1051CrossRef Zanini M, Meyer E, Simon S (2017) Pulp inflammation diagnosis from clinical to inflammatory mediators: a systematic review. J Endod 43(7):1033–1051CrossRef
10.
Zurück zum Zitat Coutaux A, Adam F, Willer JC, Le Bars D (2005) Hyperalgesia and allodynia: peripheral mechanisms. Joint Bone Spine 72(5):359–371CrossRef Coutaux A, Adam F, Willer JC, Le Bars D (2005) Hyperalgesia and allodynia: peripheral mechanisms. Joint Bone Spine 72(5):359–371CrossRef
11.
Zurück zum Zitat 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):962–969CrossRef 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):962–969CrossRef
12.
Zurück zum Zitat Rosa V, Zhang Z, Grande RH, Nör JE (2013) Dental pulp tissue engineering in full-length human root canals. J Dent Res 92(11):970–975CrossRef Rosa V, Zhang Z, Grande RH, Nör JE (2013) Dental pulp tissue engineering in full-length human root canals. J Dent Res 92(11):970–975CrossRef
13.
Zurück zum Zitat 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 17:335–339CrossRef 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 17:335–339CrossRef
14.
Zurück zum Zitat Nobuhara WK, Carnes DL, Gilles JA (1993) Anti-inflammatory effects of dexamethasone on periapical tissues following endodontic overinstrumentation. J Endod 19(10):501–507CrossRef Nobuhara WK, Carnes DL, Gilles JA (1993) Anti-inflammatory effects of dexamethasone on periapical tissues following endodontic overinstrumentation. J Endod 19(10):501–507CrossRef
15.
Zurück zum Zitat 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):376–380CrossRef 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):376–380CrossRef
17.
Zurück zum Zitat 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):25–29CrossRef 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):25–29CrossRef
18.
Zurück zum Zitat 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):651–654CrossRef 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):651–654CrossRef
19.
Zurück zum Zitat 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):203–211CrossRef 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):203–211CrossRef
20.
Zurück zum Zitat Schäfers M, Sorkin L (2008) Effect of cytokines on neuronal excitability. Neurosci Lett 437(3):188–193CrossRef Schäfers M, Sorkin L (2008) Effect of cytokines on neuronal excitability. Neurosci Lett 437(3):188–193CrossRef
21.
Zurück zum Zitat Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461CrossRef Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461CrossRef
22.
Zurück zum Zitat Marshall JG, Liesinger AW (1993) Factors associated with endodontic posttreatment pain. J Endod 19(11):573–575CrossRef Marshall JG, Liesinger AW (1993) Factors associated with endodontic posttreatment pain. J Endod 19(11):573–575CrossRef
23.
Zurück zum Zitat 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):605–615CrossRef 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):605–615CrossRef
24.
Zurück zum Zitat 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):250–255CrossRef 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):250–255CrossRef
25.
Zurück zum Zitat 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 81:171–177CrossRef 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 81:171–177CrossRef
26.
Zurück zum Zitat Albuquerque MT, Valera MC, Nakashima M, Nör JE, Bottino MC (2014) Tissue-engineering-based strategies for regenerative endodontics. J Dent Res 93(12):1222–1231CrossRef Albuquerque MT, Valera MC, Nakashima M, Nör JE, Bottino MC (2014) Tissue-engineering-based strategies for regenerative endodontics. J Dent Res 93(12):1222–1231CrossRef
27.
Zurück zum Zitat 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):38–42CrossRef 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):38–42CrossRef
28.
Zurück zum Zitat Modulevsky DJ, Cuerrier CM, Pelling AE (2016) Biocompatibility of subcutaneously implanted plant-derived cellulose biomaterials. PLoS One Jun 21:11(6) Modulevsky DJ, Cuerrier CM, Pelling AE (2016) Biocompatibility of subcutaneously implanted plant-derived cellulose biomaterials. PLoS One Jun 21:11(6)
29.
Zurück zum Zitat 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):778–785PubMed 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):778–785PubMed
30.
Zurück zum Zitat Sasaki T, Watanabe C (1995) Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 16:9e15CrossRef Sasaki T, Watanabe C (1995) Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 16:9e15CrossRef
31.
Zurück zum Zitat 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):35–40CrossRef 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):35–40CrossRef
32.
Zurück zum Zitat Pashley EL, Myers DR, Pashley DH, Whitford GM (1980) Systemic distribution of 14C-formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 59(3):602–608CrossRef Pashley EL, Myers DR, Pashley DH, Whitford GM (1980) Systemic distribution of 14C-formaldehyde from formocresol-treated pulpotomy sites. J Dent Res 59(3):602–608CrossRef
33.
Zurück zum Zitat 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):539–543CrossRef 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):539–543CrossRef
34.
Zurück zum Zitat 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):441–446CrossRef 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):441–446CrossRef
35.
Zurück zum Zitat 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):204–209CrossRef 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):204–209CrossRef
36.
Zurück zum Zitat 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 5:92–97CrossRef 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 5:92–97CrossRef
37.
Zurück zum Zitat 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 31:32–39CrossRef 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 31:32–39CrossRef
38.
Zurück zum Zitat 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):705–710CrossRef 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):705–710CrossRef
39.
Zurück zum Zitat 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):511–516CrossRef 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):511–516CrossRef
Metadaten
Titel
Transforaminal and systemic diffusion of an active agent from a zinc oxide eugenol-based endodontic sealer containing hydrocortisone—in an in vivo model
verfasst von
Davy Aubeux
Anne Valot-Salengro
Gaelle Gautier
Arnaud Malet
Fabienne Pérez
Publikationsdatum
08.05.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 12/2020
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-020-03305-5

Weitere Artikel der Ausgabe 12/2020

Clinical Oral Investigations 12/2020 Zur Ausgabe

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Zahnmedizin und bleiben Sie gut informiert – ganz bequem per eMail.