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Radioprotective role of amifostine on osteointegration of titanium implants in the tibia of rats

  • Nevra Aydemir Celep (Ataturk University, Department of Medical Pharmacology) ;
  • Hulya Kara (Ataturk University, Faculty of Veterinary, Department of Anatomy) ;
  • Elif Erbas (Ataturk University, Faculty of Veterinary, Department of Histology and Embryology) ;
  • Elif Dogan (Kastamonu University, Faculty of Veterinary, Department of Surgery)
  • Received : 2023.01.23
  • Accepted : 2023.03.22
  • Published : 2023.05.31

Abstract

Background: Titanium is the most widely used metal for bone integration, especially for cancer patients receiving ionizing radiation. This study aimed to investigate the amifostine administration that would reduce the effects of radiation on bone healing and osseointegration in rat models. Objectives: It is aimed that the application of amifostine in rats receiving radiotherapy treatment will reduce the negative effects of ionizing radiation on the bone. Methods: Thirty-five adult male Wistar rats were randomly divided into one healthy and four experimental groups. In three consecutive days, two experimental groups of rats (AMF-RT-IMP and RT-IMP) were exposed to radiation (15 Gy/3 fractions of 5 Gy each). Then the titanium implants were inserted into the left tibia. Before the radiotherapy process, a 200 mg/kg dose of amifostine (AMF) was administered to the rats in the AMF-IMP and AMF-RT-IMP groups. Twenty-eight days after the screw implant, all rats were sacrificed, and their blood samples and tibia bones were collected for analysis. Results: The results indicated an accelerated bone formation and a more rapid healing process in the screw implants in the AMF-IMP, AMF-RT-IMP, and AMF-RT groups than in the RT-IMP group. Also, bone-implant contact area measurement and inflammation decreased with amifostine treatment in the implants subjected to irradiation (p < 0.05). Conclusions: The results obtained in the present study suggested that amifostine prevents the losses of bone minerals, bone integrity, and implant position from ionizing-radiation when given before exposure.

Keywords

References

  1. Huang EY, Wang FS, Chen YM, Chen YF, Wang CC, Lin IH, et al. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation. Oncotarget. 2014;5(20):9756-9769. https://doi.org/10.18632/oncotarget.2386
  2. Felice PA, Ahsan S, Perosky JE, Deshpande SS, Nelson NS, Donneys A, et al. Prophylactic amifostine preserves the biomechanical properties of irradiated bone in the murine mandible. Plast Reconstr Surg. 2014;133(3):314e-321e. https://doi.org/10.1097/01.prs.0000438454.29980.f8
  3. Esser E, Wagner W. Dental implants following radical oral cancer surgery and adjuvant radiotherapy. Int J Oral Maxillofac Implants. 1997;12(4):552-557. PUBMED 
  4. Andreassen CN, Grau C, Lindegaard JC. Chemical radioprotection: a critical review of amifostine as a cytoprotector in radiotherapy. Semin Radiat Oncol. 2003;13(1):62-72. https://doi.org/10.1053/srao.2003.50006
  5. Tchanque-Fossuo CN, Donneys A, Deshpande SS, Nelson NS, Boguslawski MJ, Gallagher KK, et al. Amifostine remediates the degenerative effects of radiation on the mineralization capacity of the murine mandible. Plast Reconstr Surg. 2012;129(4):646e-655e. https://doi.org/10.1097/PRS.0b013e3182454352
  6. Monson LA, Farberg AS, Jing XL, Tchanque-Fossuo CN, Donneys A, Buchman SR. Distraction osteogenesis in the rat mandible following radiation and treatment with amifostine. Plast Reconstr Surg. 2010;125(6 Suppl):41.
  7. Donneys A, Tchanque-Fossuo CN, Blough JT, Nelson NS, Deshpande SS, Buchman SR. Amifostine preserves osteocyte number and osteoid formation in fracture healing following radiotherapy. J Oral Maxillofac Surg. 2014;72(3):559-566. https://doi.org/10.1016/j.joms.2013.09.006
  8. Tchanque-Fossuo CN, Gong B, Poushanchi B, Donneys A, Sarhaddi D, Gallagher KK, et al. Raman spectroscopy demonstrates amifostine induced preservation of bone mineralization patterns in the irradiated murine mandible. Bone. 2013;52(2):712-717. https://doi.org/10.1016/j.bone.2012.07.029
  9. Gong B, Oest ME, Mann KA, Damron TA, Morris MD. Raman spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation. Bone. 2013;57(1):252-258. https://doi.org/10.1016/j.bone.2013.08.014
  10. Park C, Papiez L, Zhang S, Story M, Timmerman RD. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70(3):847-852. https://doi.org/10.1016/j.ijrobp.2007.10.059
  11. Kose O, Arabaci T, Kizildag A, Erdemci B, Ozkal Eminoglu D, Gedikli S, et al. Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis. J Periodontal Res. 2017;52(3):438-446. https://doi.org/10.1111/jre.12409
  12. de Morais JA, Trindade-Suedam IK, Pepato MT, Marcantonio E Jr, Wenzel A, Scaf G. Effect of diabetes mellitus and insulin therapy on bone density around osseointegrated dental implants: a digital subtraction radiography study in rats. Clin Oral Implants Res. 2009;20(8):796-801. https://doi.org/10.1111/j.1600-0501.2009.01716.x
  13. de Molon RS, Morais-Camilo JA, Verzola MH, Faeda RS, Pepato MT, Marcantonio E Jr. Impact of diabetes mellitus and metabolic control on bone healing around osseointegrated implants: removal torque and histomorphometric analysis in rats. Clin Oral Implants Res. 2013;24(7):831-837. https://doi.org/10.1111/j.1600-0501.2012.02467.x
  14. Arabaci T, Kermen E, Ozkanlar S, Kose O, Kara A, Kizildag A, et al. Therapeutic effects of melatonin on alveolar bone resorption after experimental periodontitis in rats: a biochemical and immunohistochemical study. J Periodontol. 2015;86(7):874-881. https://doi.org/10.1902/jop.2015.140599
  15. Cornelison JB, Isaac CV, Devota CJ, Billian J, Brown TT, deJong JL, et al. A comparison of three decalcification agents for assessments of cranial fracture histomorphology. J Forensic Sci. 2022;67(3):1157-1166. https://doi.org/10.1111/1556-4029.14990
  16. Yildiz A, Esen E, Kurkcu M, Damlar I, Daglioglu K, Akova T. Effect of zoledronic acid on osseointegration of titanium implants: an experimental study in an ovariectomized rabbit model. J Oral Maxillofac Surg. 2010;68(3):515-523. https://doi.org/10.1016/j.joms.2009.07.066
  17. Robertson WW Jr, Butler MS, D'Angio GJ, Rate WR. Leg length discrepancy following irradiation for childhood tumors. J Pediatr Orthop. 1991;11(3):284-287. https://doi.org/10.1097/01241398-199105000-00002
  18. Wang R, Pillai K, Jones PK. Dosimetric measurement of scattered radiation from dental implants in simulated head and neck radiotherapy. Int J Oral Maxillofac Implants. 1998;13(2):197-203.
  19. Damron TA, Spadaro JA, Margulies B, Damron LA. Dose response of amifostine in protection of growth plate function from irradiation effects. Int J Cancer. 2000;90(2):73-79. https://doi.org/10.1002/(SICI)1097-0215(20000420)90:2<73::AID-IJC3>3.0.CO;2-E
  20. Damron TA, Spadaro JA, Tamurian RM, Damron LA. Sparing of radiation-induced damage to the physis: fractionation alone compared to amifostine pretreatment. Int J Radiat Oncol Biol Phys. 2000;47(4):1067-1071. https://doi.org/10.1016/S0360-3016(00)00511-3
  21. Kopjar N, Miocic S, Ramic S, Milic M, Viculin T. Assessment of the radioprotective effects of amifostine and melatonin on human lymphocytes irradiated with gamma-rays in vitro. Arh Hig Rada Toksikol 2006;57(2):155-163. 
  22. Kouloulias VE, Kouvaris JR, Kokakis JD, Kostakopoulos A, Mallas E, Metafa A, et al. Impact on cytoprotective efficacy of intermediate interval between amifostine administration and radiotherapy: a retrospective analysis. Int J Radiat Oncol Biol Phys. 2004;59(4):1148-1156. https://doi.org/10.1016/j.ijrobp.2003.12.013
  23. Sommer NG, Hahn D, Okutan B, Marek R, Weinberg AM. Animal models in orthopedic research: the proper animal model to answer fundamental questions on bone healing depending on pathology and implant material. In: Tvrda E, Yenisetti S, editors. Animal Models in Medicine and Biology. London: IntechOpen Limited; 2019. 
  24. Ramdas J, Warrier RP, Scher C, Larussa V. Effects of amifostine on clonogenic mesenchymal progenitors and hematopoietic progenitors exposed to radiation. J Pediatr Hematol Oncol. 2003;25(1):19-26. https://doi.org/10.1097/00043426-200301000-00006
  25. Srinivasan V, Pendergrass JA Jr, Kumar KS, Landauer MR, Seed TM. Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine) pellets. Int J Radiat Biol. 2002;78(6):535-543. https://doi.org/10.1080/095530002317577358
  26. Cassatt DR, Fazenbaker CA, Bachy CM, Kifle G, McCarthy MP. Amifostine (ETHYOL) protects rats from mucositis resulting from fractionated or hyperfractionated radiation exposure. Int J Radiat Oncol Biol Phys. 2005;61(3):901-907. https://doi.org/10.1016/j.ijrobp.2004.10.032
  27. Tchanque-Fossuo CN, Donneys A, Razdolsky ER, Monson LA, Farberg AS, Deshpande SS, et al. Quantitative histologic evidence of amifostine-induced cytoprotection in an irradiated murine model of mandibular distraction osteogenesis. Plast Reconstr Surg. 2012;130(6):1199-1207. https://doi.org/10.1097/PRS.0b013e31826d2201
  28. Al-Tamemi EI. Analysis of inflammatory cells in osseointegration of CpTi implant radiated by low level laser therapy. J Baghdad Coll Dent. 2015;27(1):105-110. https://doi.org/10.12816/0015273