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Brazilian propolis wax as an anti-type-IV-hypersensitivity agent in metal bracket orthodontic treatment

  • Grahita Aditya ,
  • Oedijani Santoso ,
  • Lisyani Budipradigdo Suromo ,


Background: Nickel (Ni2+) allergy on the mucosa and gingiva is frequently found in patients with fixed metal orthodontic treatment as the manifestation of type-IV hypersensitivity reactions.

Method: This study aims to observe the effect of Brazilian propolis wax on salivary Ni2+ ion levels and blood serum IFN-γ and IL-10 levels during fixed metal bracket orthodontic treatment. A total of 34 New Zealand rabbits were divided into three groups. Before the treatment, Ni2+sensitization was done using a 125 μL NiCl2 injection. Metal brackets were placed on the four anterior teeth for 28 days. Saliva was carried out for Ni2+ ion level analysis by inductively coupled plasma-optical emission spectrometry (ICP-OES), and ELISA measured peripheral blood serum for IFN-γ and IL-10 level analysis.

Result: Ni2+ ion release in the control group showed a higher expression than in the wax and propolis-wax groups. IFN-γ expression level is reduced in the wax and propolis-wax group than in the control group. Moreover, a significantly different IL-10 expression was also observed in the wax and propolis-wax groups.

Conclusion: The combination of propolis into wax orthodontic inhibits Ni2+ ion release by promoting anti-inflammatory IL-10 expression.


  1. Graham-Brown R, Harman K, Johnston G. Dermatology. John Wiley & Sons; 2016.
  2. Leite LP, Bell RA. Adverse hypersensitivity reactions in orthodontics. Semin Orthod. 2004;10(4):240–3. Available from:
  3. Bordignon V, Palamara F, Cordiali-Fei P, Vento A, Aiello A, Picardo M, et al. Nickel, palladium and rhodium induced IFN-gamma and IL-10 production as assessed by in vitro ELISpot-analysis in contact dermatitis patients. BMC Immunol. 2008;9:19. Available from:
  4. Gomez-Casado C, Sanchez-Solares J, Izquierdo E, Díaz-Perales A, Barber D, Escribese MM. Oral Mucosa as a Potential Site for Diagnosis and Treatment of Allergic and Autoimmune Diseases. Foods (Basel, Switzerland). 2021;10(5):970. Available from:
  5. Makihira S, Mine Y, Nikawa H, Shuto T, Iwata S, Hosokawa R, et al. Titanium ion induces necrosis and sensitivity to lipopolysaccharide in gingival epithelial-like cells. Toxicol Vitr. 2010;24(7):1905–10. Available from:
  6. Salvetr P, Školáková A, Šulcová L, Kačenka Z, Kadlecová B, Novák P. Effect of Zirconium, Niobium and Chromium on Structure and Properties of Ni-Ti Alloy. Manuf Technol. 2018;18(5):817–20. Available from:
  7. Denizoğlu S, Duymuş ZY, Akyalçin Ş. Evaluation of Ion Release from Two Base-Metal Alloys at Various pH Levels. J Int Med Res. 2004;32(1):33–8. Available from:
  8. Genchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020;17(3):679. Available from:
  9. Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21(11):739–51. Available from:
  10. Faccioni F, Franceschetti P, Cerpelloni M, Fracasso ME. In vivo study on metal release from fixed orthodontic appliances and DNA damage in oral mucosa cells. Am J Orthod Dentofac Orthop. 2003;124(6):687–93. Available from:
  11. Kummer A. Cleft Palate and Craniofacial Anomalies: Effects on Speech and Resonance. 2nd ed. Thomas Dalmar Learning; 2008. 243 p.
  12. Roediger B, Weninger W. How nickel turns on innate immune cells. Immunol & Cell Biol. 2010;89(1):1–2. Available from:
  13. Colagiovanni A, Di Renzo L, Sarlo F, Schiavino D, De Lorenzo A. Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization. Eur Rev Med Pharmacol Sci. 2016;20(12):2663–6.
  14. Liew KY, Kamise NI, Ong HM, Aw Yong PY, Islam F, Tan JW, et al. Anti-Allergic Properties of Propolis: Evidence From Preclinical and Clinical Studies. Front Pharmacol. 2022;12:785371. Available from:
  15. Dilokthornsakul W, Kosiyaporn R, Wuttipongwaragon R, Dilokthornsakul P. Potential effects of propolis and honey in COVID-19 prevention and treatment: A systematic review of in silico and clinical studies. J Integr Med. 2022/01/31. 2022;20(2):114–25. Available from:
  16. Magnavacca A, Sangiovanni E, Racagni G, Dell’Agli M. The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases. Med Res Rev. 2021/11/02. 2022;42(2):897–945. Available from:
  17. Hata T, Tazawa S, Ohta S, Rhyu M-R, Misaka T, Ichihara K. Artepillin C, a major ingredient of Brazilian propolis, induces a pungent taste by activating TRPA1 channels. PLoS One. 2012/11/02. 2012;7(11):e48072–e48072. Available from:
  18. Conte FL, Pereira AC, Brites G, Ferreira I, Silva AC, Sebastião AI, et al. Exploring the antioxidant, anti-inflammatory and antiallergic potential of Brazilian propolis in monocytes. Phytomedicine Plus. 2022;2(2):100231. Available from:
  19. Zulhendri F, Perera CO, Tandean S, Abdulah R, Herman H, Christoper A, et al. The Potential Use of Propolis as a Primary or an Adjunctive Therapy in Respiratory Tract-Related Diseases and Disorders: A Systematic Scoping Review. Biomed & Pharmacother. 2022;146:112595. Available from:
  20. Dolabella LMP, Oliveira JG, Lins V, Matencio T, Vasconcelos WL. Ethanol extract of propolis as a protective coating for mild steel in chloride media. J Coatings Technol Res. 2016;13(3):543–55. Available from:
  21. Park YK, Paredes-Guzman JF, Aguiar CL, Alencar SM, Fujiwara FY. Chemical Constituents in Baccharis dracunculifolia as the Main Botanical Origin of Southeastern Brazilian Propolis. J Agric Food Chem. 2004;52(5):1100–3. Available from:
  22. Piñeros AR, de Lima MHF, Rodrigues T, Gembre AF, Bertolini TB, Fonseca MD, et al. Green propolis increases myeloid suppressor cells and CD4+Foxp3+ cells and reduces Th2 inflammation in the lungs after allergen exposure. J Ethnopharmacol. 2020;252:112496. Available from:
  23. Szliszka E, Kucharska AZ, Sokół-Łętowska A, Mertas A, Czuba ZP, Król W. Chemical Composition and Anti-Inflammatory Effect of Ethanolic Extract of Brazilian Green Propolis on Activated J774A.1 Macrophages. Evid Based Complement Alternat Med. 2013/06/06. 2013;2013:976415. Available from:
  24. Kumarasinghe LS, Ninan N, Dabare PRL, Cavallaro A, Doğramacı EJ, Rossi-Fedele G, et al. Bioactive Plasma Coatings on Orthodontic Brackets: In Vitro Metal Ion Release and Cytotoxicity. Coatings. 2021;11(7):857. Available from:
  25. Oka A, Okano M. Relationship between Saliva and Sublingual Immunotherapy. Pathog (Basel, Switzerland). 2021;10(11):1358. Available from:
  26. Narmada IB, Sudarno NT, Sjafei A, Setiyorini Y. The influence of artificial salivary pH on nickel ion release and the surface morphology of stainless steel bracket-nickel-titanium archwire combinations. Dent J (Majalah Kedokt Gigi). 2017;50(2):80. Available from:
  27. Yunizar MF, Watanabe M, Liu L, Minami N, Ichikawa T. Metal Allergy Mediates the Development of Oral Lichen Planus via TSLP-TSLPR Signaling. J Clin Med. 2022;11(3):519. Available from:
  28. Lin C-W, Hsieh P-Y, Chou C-M, Chung C-J, He J-L. Femtosecond laser surface roughening and pulsed plasma polymerization duplex treatment on medical-grade stainless steel substrates for orthodontic purpose. Surf Coatings Technol. 2021;427:127819. Available from:
  29. Matos de Souza R, Macedo de Menezes L. Nickel, Chromium and Iron Levels in the Saliva of Patients with Simulated Fixed Orthodontic Appliances. Angle Orthod. 2008;78(2):345–50. Available from:
  30. Orsi RDO, Barros DCB, Silva RDCM, Queiroz JV de, Araújo WL de P, Shinohara AJ. Toxic Metals in the Crude Propolis and Its Transfer Rate to the Ethanolic Extract. Sociobiology. 2018;65(4):640. Available from:
  31. Zulhendri F, Chandrasekaran K, Kowacz M, Ravalia M, Kripal K, Fearnley J, et al. Antiviral, Antibacterial, Antifungal, and Antiparasitic Properties of Propolis: A Review. Foods (Basel, Switzerland). 2021;10(6):1360. Available from:
  32. Okereke CJ, Onyenegecha CP, Njoku IJ. Corrosion Susceptibility of Stainless Steel in Artificial Saliva Containing Citric Acid [Internet]. Research Square Platform LLC; 2021. Available from:
  33. Braakhuis A. Evidence on the Health Benefits of Supplemental Propolis. Nutrients. 2019;11(11):2705. Available from:
  34. ORSI RO, FUNARI SRC, SOARES AMVC, CALVI SA, OLIVEIRA SL, SFORCIN JM, et al. Immunomodulatory action of propolis on macrophage activation. J Venom Anim Toxins. 2000;6(2):205–19. Available from:
  35. Sá-Nunes A, Faccioli LH, Sforcin JM. Propolis: lymphocyte proliferation and IFN-γ production. J Ethnopharmacol. 2003;87(1):93–7. Available from:
  36. Bhargava P, Mahanta D, Kaul A, Ishida Y, Terao K, Wadhwa R, et al. Experimental Evidence for Therapeutic Potentials of Propolis. Nutrients. 2021;13(8):2528. Available from:
  37. Machado JL, Assunção AKM, da Silva MCP, Dos Reis AS, Costa GC, Arruda D de S, et al. Brazilian green propolis: anti-inflammatory property by an immunomodulatory activity. Evid Based Complement Alternat Med. 2012/12/19. 2012;2012:157652. Available from:
  38. Minang JT, Areström I, Zuber B, Jönsson G, Troye-Blomberg M, Ahlborg N. Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel. Clin Exp Immunol. 2006;143(3):494–502. Available from:
  39. Oka A, Kidoguchi M, Kariya S, Fujiwara T, Yuta A, Miyashita H, et al. Role of salivary microbiome in IL‐10 production and efficacy of sublingual immunotherapy. Allergy. 2021;76(8):2617–20. Available from:

How to Cite

Grahita Aditya, Oedijani Santoso, & Lisyani Budipradigdo Suromo. (2022). Brazilian propolis wax as an anti-type-IV-hypersensitivity agent in metal bracket orthodontic treatment. Bali Medical Journal, 11(3), 2052–2056.




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Grahita Aditya
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Oedijani Santoso
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Lisyani Budipradigdo Suromo
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