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Systemic and local effects of doxycycline and low-intensity laser treatment on periodontitis in rats

  • Received : 2021.01.19
  • Accepted : 2021.07.15
  • Published : 2022.02.28

Abstract

Purpose: This study evaluated the systemic and local effects of doxycycline (DOX) and low-intensity laser (LIL) treatment as adjuvants to scaling and root planing (SRP) in the treatment of experimental periodontitis in rats. Methods: The sample consisted of 180 male rats (Rattus norvegicus albinus, Wistar), of which 30 did not receive induction of periodontal disease (negative control [NC] group) and 150 received induction of periodontal disease in the lower first molar. After 7 days, the ligature was removed, and the animals were divided into the following groups: NT (no treatment), SRP (SRP), DOX (SRP and DOX irrigation), LIL (SRP and laser irradiation), and DOX+LIL (SRP, DOX, and LIL). The animals were euthanized at 7, 15, and 30 days; thereafter, biochemical, radiographic, histological, and immunohistochemical analyses were performed. Results: In the intragroup analysis, lower concentrations of α-1-glycoprotein acid (α-1-Ga) and complement 3 (C3) were observed in the DOX+LIL group than in all other groups at all time points, as well as lower levels of complement 4 (C4) at 15 and 30 days (P<0.001). Less bone loss was observed in the DOX, LIL, and DOX+LIL groups than in the NC and SRP groups at all time points (P<0.001). There was a smaller number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the DOX+LIL group than in the other groups at all time points (P<0.001). Positive correlations were observed between the systemic levels of α-1-Ga, C3, and C4 and the number of TRAP-positive cells. Conclusions: The combination of DOX with LIL as SRP adjuvants was effective both systemically and locally for the treatment of experimental periodontitis in rats.

Keywords

Acknowledgement

We are grateful to the Dentistry Faculties of the Federal University of Alfenas (UNIFAL-MG) and the State University of Sao Paulo (UNESP), Aracatuba campus, for providing the physical space for the work.

References

  1. Mann J, Bernstein Y, Findler M. Periodontal disease and its prevention, by traditional and new avenues. Exp Ther Med 2020;19:1504-6.
  2. Irani S, Barati I, Badiei M. Periodontitis and oral cancer - current concepts of the etiopathogenesis. Oncol Rev 2020;14:465.
  3. Yang NY, Zhou Y, Zhao HY, Liu XY, Sun Z, Shang JJ. Increased interleukin 1α and interleukin 1β expression is involved in the progression of periapical lesions in primary teeth. BMC Oral Health 2018;18:124. https://doi.org/10.1186/s12903-018-0586-3
  4. Lourenco AH, Torres AL, Vasconcelos DP, Ribeiro-Machado C, Barbosa JN, Barbosa MA, et al. Osteogenic, anti-osteoclastogenic and immunomodulatory properties of a strontium-releasing hybrid scaffold for bone repair. Mater Sci Eng C Mater Biol Appl 2019;99:1289-303. https://doi.org/10.1016/j.msec.2019.02.053
  5. Izuora KE, Ezeanolue EE, Neubauer MF, Gewelber CL, Allenback GL, Shan G, et al. Changes in inflammatory and bone turnover markers after periodontal disease treatment in patients with diabetes. Am J Med Sci 2016;351:589-94. https://doi.org/10.1016/j.amjms.2016.02.004
  6. Caffesse RG, Echeverria JJ. Treatment trends in periodontics. Periodontol 2000 2019;79:7-14. https://doi.org/10.1111/prd.12245
  7. Teughels W, Feres M, Oud V, Martin C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: a systematic review and meta-analysis. J Clin Periodontol 2020;47 Suppl 22:257-81.
  8. Zhao H, Hu J, Zhao L. Adjunctive subgingival application of Chlorhexidine gel in nonsurgical periodontal treatment for chronic periodontitis: a systematic review and meta-analysis. BMC Oral Health 2020;20:34. https://doi.org/10.1186/s12903-020-1021-0
  9. Dalcico R, de Menezes AM, Deocleciano OB, Oria RB, Vale ML, Ribeiro RA, et al. Protective mechanisms of simvastatin in experimental periodontal disease. J Periodontol 2013;84:1145-57. https://doi.org/10.1902/jop.2012.120114
  10. Ting M, Whitaker EJ, Albandar JM. Systematic review of the in vitro effects of statins on oral and perioral microorganisms. Eur J Oral Sci 2016;124:4-10. https://doi.org/10.1111/eos.12239
  11. Chambrone L, Vargas M, Arboleda S, Serna M, Guerrero M, de Sousa J, et al. Efficacy of local and systemic antimicrobials in the non-surgical treatment of smokers with chronic periodontitis: a systematic review. J Periodontol 2016;87:1320-32. https://doi.org/10.1902/jop.2016.160268
  12. Lecio G, Ribeiro FV, Pimentel SP, Reis AA, da Silva RVC, Nociti-Jr F, et al. Novel 20% doxycycline-loaded PLGA nanospheres as adjunctive therapy in chronic periodontitis in type-2 diabetics: randomized clinical, immune and microbiological trial. Clin Oral Investig 2020;24:1269-79. https://doi.org/10.1007/s00784-019-03005-9
  13. Passanezi E, Damante CA, de Rezende ML, Greghi SL. Lasers in periodontal therapy. Periodontol 2000 2015;67:268-91. https://doi.org/10.1111/prd.12067
  14. Swerts AA, Santos BFE, Bruzadelli SR, Brigagao MRPL, Lima DC, Fernandes LA. Treatment of experimental periodontal disease by laser therapy in simvastatin-modified rats. J Appl Oral Sci 2017;25:387-95. https://doi.org/10.1590/1678-7757-2016-0467
  15. De Almeida J, Ervolino E, Bonfietti LH, Novaes VC, Theodoro LH, Fernandes LA, et al. Adjuvant therapy with sodium alendronate for the treatment of experimental periodontitis in rats. J Periodontol 2015;86:1166-75. https://doi.org/10.1902/jop.2015.150166
  16. Gorle AP, Khairnar DP. An approach to improve therapeutic efficacy of doxycycline hyclate in treatment of periodontitis. Iran J Pharm Res 2018;17:1550-62.
  17. Kalinichenko LS, Koplik EV, Pertsov SS. Cytokine profile of peripheral blood in rats with various behavioral characteristics during acute emotional stress. Bull Exp Biol Med 2014;156:441-4. https://doi.org/10.1007/s10517-014-2369-4
  18. Mbuyi JB, Dequeker J. Biochemical analyses of EDTA extracts and collagenase digests from bone and skin of Wistar rats. Lab Anim 1982;16:256-64. https://doi.org/10.1258/002367782780891714
  19. Santos BF, Souza EQ, Brigagao MR, Lima DC, Fernandes LA. Local application of statins in the treatment of experimental periodontal disease in rats. J Appl Oral Sci 2017;25:168-76. https://doi.org/10.1590/1678-77572016-0149
  20. Fernandes LA, de Almeida JM, Theodoro LH, Bosco AF, Nagata MJH, Martins TM, et al. Treatment of experimental periodontal disease by photodynamic therapy in immunosuppressed rats. J Clin Periodontol 2009;36:219-28. https://doi.org/10.1111/j.1600-051X.2008.01355.x
  21. Garcia VG, Fernandes LA, Macarini VC, de Almeida JM, Martins TM, Bosco AF, et al. Treatment of experimental periodontal disease with antimicrobial photodynamic therapy in nicotine-modified rats. J Clin Periodontol 2011;38:1106-14. https://doi.org/10.1111/j.1600-051X.2011.01785.x
  22. Theodoro LH, Pires JR, Fernandes LA, Gualberto Junior EC, Longo M, de Almeida JM, et al. Effect of antimicrobial photodynamic therapy on periodontally infected tooth sockets in rats. Lasers Med Sci 2015;30:677-83. https://doi.org/10.1007/s10103-013-1400-8
  23. Madi M, Pavlic V, Samy W, Alagl A. The anti-inflammatory effect of locally delivered nano-doxycycline gel in therapy of chronic periodontitis. Acta Odontol Scand 2018;76:71-6. https://doi.org/10.1080/00016357.2017.1385096
  24. Trajano VCDC, Brasileiro CB, Henriques JAS, Cota LM, Lanza CR, Cortes ME. Doxycycline encapsulated in β-cyclodextrin for periodontitis: a clinical trial. Braz Oral Res 2020;33:e112. https://doi.org/10.1590/1807-3107bor-2019.vol33.0112
  25. Dengizek Eltas S, Gursel M, Eltas A, Alptekin NO, Ataoglu T. Evaluation of long-term effects of diode laser application in periodontal treatment of poorly controlled type 2 diabetic patients with chronic periodontitis. Int J Dent Hyg 2019;17:292-9. https://doi.org/10.1111/idh.12384
  26. Rosero KAV, Sampaio RMF, Deboni MCZ, Correa L, Marques MM, Ferraz EP, et al. Photobiomodulation as an adjunctive therapy for alveolar socket preservation: a preliminary study in humans. Lasers Med Sci 2020;35:1711-20. https://doi.org/10.1007/s10103-020-02962-y
  27. Cerdeira CD, Lima Brigagao MRPL, Carli ML, de Souza Ferreira C, de Oliveira Isac Moraes G, Hadad H, et al. Low-level laser therapy stimulates the oxidative burst in human neutrophils and increases their fungicidal capacity. J Biophotonics 2016;9:1180-8. https://doi.org/10.1002/jbio.201600035
  28. Dehdashtizadeh A, Esnaashari N, Farhad SZ, Ejeian F, Amini S. The effect of laser irradiation and doxycycline application on the production of matrix metalloproteinase-8 and collagen I from cultured human periodontal ligament cells. Dent Res J (Isfahan) 2020;17:213-8. https://doi.org/10.4103/1735-3327.284732
  29. Nastri L, De Rosa A, De Gregorio V, Grassia V, Donnarumma G. A new controlled-release material containing metronidazole and doxycycline for the treatment of periodontal and peri-implant diseases: formulation and in vitro testing. Int J Dent 2019;2019:9374607. https://doi.org/10.1155/2019/9374607
  30. Gamal AY, Kumper RM, Al Gendy AR. Doxycycline-loaded β-tricalcium phosphate release following EDTA root surface etching improved the clinical outcomes in chronic periodontitis: an in vivo study. J Periodontol 2013;84:924-33. https://doi.org/10.1902/jop.2012.120343
  31. Khandan A, Ozada N, Karamian E. Novel microstructure mechanical activated nanocomposites for tissue engineering applications. J Bioeng Biomed Sci 2015;5:1-4.
  32. Kim TS, Klimpel H, Fiehn W, Eickholz P. Comparison of the pharmacokinetic profiles of two locally administered doxycycline gels in crevicular fluid and saliva. J Clin Periodontol 2004;31:286-92. https://doi.org/10.1111/j.0303-6979.2004.00494.x
  33. Heidari M, Paknejad M, Jamali R, Nokhbatolfoghahaei H, Fekrazad R, Moslemi N. Effect of laser photobiomodulation on wound healing and postoperative pain following free gingival graft: a split-mouth triple-blind randomized controlled clinical trial. J Photochem Photobiol B 2017;172:109-14. https://doi.org/10.1016/j.jphotobiol.2017.05.022
  34. Wang B, Booij-Vrieling HE, Bronkhorst EM, Shao J, Kouwer PH, Jansen JA, et al. Antimicrobial and anti-inflammatory thermo-reversible hydrogel for periodontal delivery. Acta Biomater 2020;116:259-67. https://doi.org/10.1016/j.actbio.2020.09.018
  35. Zhang L, Chen W, Li Y, Hong W, Li H, Cui Z, et al. Effect of 650-nm low-level laser irradiation on c-Jun, c-Fos, ICAM-1, and CCL2 expression in experimental periodontitis. Lasers Med Sci 2020;35:31-40. https://doi.org/10.1007/s10103-018-2662-y
  36. Puturidze S, Margvelashvili M, Bilder L, Kalandadze M, Margvelashvili V. Correlation of oral health status with general health in elderly living at residential homes in Georgia. Georgian Med News 2019;292-293:21-5.
  37. Hajishengallis G, Kajikawa T, Hajishengallis E, Maekawa T, Reis ES, Mastellos DC, et al. Complement-dependent mechanisms and interventions in periodontal disease. Front Immunol 2019;10:406. https://doi.org/10.3389/fimmu.2019.00406
  38. Rasperini G, Pellegrini G, Sugai J, Mauro C, Fiocchi S, Corvi Mora P, et al. Effects of food supplements on periodontal status and local and systemic inflammation after nonoperative periodontal treatment. J Oral Sci 2019;61:213-20. https://doi.org/10.2334/josnusd.18-0048
  39. Li F, Xu HS. Effects of low level laser combined with basic periodontal therapy on cytokines and LPS, leptin in gingival crevicular fluid of diabetes mellitus complicated with chronic periodontitis patients. Shanghai Kou Qiang Yi Xue 2018;27:637-40.
  40. Joshi A, Maddipati S, Chatterjee A, Lihala R, Gupta A. Gingival crevicular fluid resistin levels in chronic periodontitis with type 2 diabetes before and after non-surgical periodontal therapy: a clinico-biochemical study. Indian J Dent Res 2019;30:47-51.