AVALIAÇÃO HISTOLÓGICA DE FERIDAS CUTÂNEAS DE RATOS SUBMETIDAS À FOTOBIOMODULAÇÃO LASER E OZONIOTERAPIA

Resumo

As terapias biomoduladoras tem sido cada vez mais utilizadas na área da saúde para estimular o reparo tecidual. Este estudo objetivou avaliar comparativamente os efeitos da fotobiomodulação laser, ozônio gasoso e óleo ozonizado sobre o reparo tecidual, através da análise histológica de feridas cutâneas de ratos. Quarenta ratos Wistar foram alocados randomicamente em quatro grupos de dez animais cada: Grupo controle (GC), Laser (GL), Gás Ozônio (GGO) e Óleo Ozonizado (GOO). Foram realizados ferimentos cutâneos padronizados no dorso dos animais e os grupos experimentais foram tratados por três dias consecutivos. Cinco e dez dias após a cirurgia, cinco ratos de cada grupo foram eutanasiados e foram coletadas amostras da área da ferida para processamento histológico e coloração com Hematoxilina-eosina e Sírius vermelho. Com cinco micrografias padrão de cada secção histológica, foram avaliadas celularidade do tecido de granulação, expressão do colágeno e densidade vascular. O nível de significância foi de p<0,05. Dez dias após a cirurgia, constatou-se um aumento da celularidade do tecido de granulação em todos os grupos, exceto no GGO (p=0,043). Foi observada uma diferença estatisticamente significativa em relação à organização do colágeno entre o GC e o GL no 5o dia (p=0,012). A densidade vascular foi maior no GOO em relação aos demais grupos experimentais no 5o (p=0,045) e no 10o dia (p=0,004). Na forma de gás, o ozônio atenuou o processo inflamatório crônico, enquanto na forma de óleo se destacou pelo aumento da vascularização nos dois períodos do estudo. O grupo fotobiomodulado apresentou melhor organização do colágeno.

Biografia do Autor

Flávia Quadros Lima, EBMSP

Cirurgiã-dentista. Mestre em Medicina e Saúde Humana pela Escola Bahiana de Medicina e Saúde Pública.

Antônio Márcio Marchionni, EBMSP

Cirurgião Bucomaxifacial. Doutor em Fotobiomodulação pela Universidade Federal da Bahia.

Beatriz Paim de Figueiredo Braitenbach, UFBA

Nutricionista. Aluna de Mestrado do Programa de Pós-graduação Processos Interativos dos Órgãos e Sistemas.

Bruna Carvalho Lopez Moreno, EBMSP

Graduação em Odontologia, Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia.

Sarah Souza Lima, UFBA

Bacharel em Saúde. Aluna de Doutorado do Programa de Pós-graduação Processos Interativos dos Órgãos e Sistemas.

Carla Barreto Cerqueira, UFBA

Bacharel em Saúde. Fisioterapeuta. Aluna de Doutorado do Programa de Pós-graduação em Processos Interativos dos Órgãos e Sistemas.

Referências

1. Cerqueira CBS, Dantas JBL, Souza BGS, Carvalho MA, Medrado ARAP, Matos JBTL. Tissue repair under the influence of plasma jet and other biomodulator therapies - state of the art. Res Soc Dev. 2022;11(12):e470111234870. Available from: https://doi.org/10.33448/rsd-v11i12.34870 DOI: https://doi.org/10.33448/rsd-v11i12.34870 DOI: https://doi.org/10.33448/rsd-v11i12.34870

2. Özalp ÖA, Sindel MA, Altay IH, Özbudak B, Bilgin B, Kocabalkan B, et al. Comparative evaluation of the efficacy of ozone therapy and low level laser therapy on oral mucosal wound healing in rat experimental model. J Stomatol Oral Maxillofac Surg. 2022;123(6):e670-e674. Available from: https://doi.org/10.1016/j.jormas.2022.03.018 DOI: https://doi.org/10.1016/j.jormas.2022.03.018 DOI: https://doi.org/10.1016/j.jormas.2022.03.018

3. Nesi-Reis V, Lera-Nonose DSSL, Oyama J, Silva-Lalucci MPP, Demarchi IG, Aristides SMA, et al. Contribution of photodynamic therapy in wound healing: A systematic review. Photodiagnosis Photodyn Ther. 2018;21:294-305. Available from: DOI: https://doi.org/10.1016/j.pdpdt.2017.12.015 DOI: https://doi.org/10.1016/j.pdpdt.2017.12.015

4. Besser M, Schaeler L, Plattfaut I, Brill FHH, Kampe A, Geffken M, et al. Pulsed low-intensity laser treatment stimulates wound healing without enhancing biofilm development in vitro. J Photochem Photobiol B. 2022;233:112504. Available from: https://doi.org/10.1016/j.jphotobiol.2022.112504 DOI: https://doi.org/10.1016/j.jphotobiol.2022.112504 DOI: https://doi.org/10.1016/j.jphotobiol.2022.112504

5. de Castro JR, da Silva Pereira F, Chen L, Arana-Chavez VE, Ballester RY, DiPietro LA. Improvement of full-thickness rat skin wounds by photobiomodulation therapy (PBMT): A dosimetric study. J Photochem Photobiol B. 2020;206:111850. Available from: https://doi.org/10.1016/j.jphotobiol.2020.111850 DOI: https://doi.org/10.1016/j.jphotobiol.2020.111850 DOI: https://doi.org/10.1016/j.jphotobiol.2020.111850

6. Hänninen K. Contribution of excited ozone and oxygen molecules to the formation of the stratospheric ozone layer. Environ Ecol Res. 2019;7(3):121-134. Available from: https://www.hrpub.org/journals/article_info.php?aid=7920 DOI: https://doi.org/10.13189/eer.2019.070302 DOI: https://doi.org/10.13189/eer.2019.070302

7. Smith NL, Wilson AL, Gandhi J, Vatsia S, Khan AS. Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Med Gas Res. 2017;7(3):212-219. Available from: https://doi.org/10.4103/2045-9912.215752 DOI: https://doi.org/10.4103/2045-9912.215752 DOI: https://doi.org/10.4103/2045-9912.215752

8. Alan H, Vardi N, Özgür C, Hüseyin A, Yolcu Ü, Doğan DÖ. Comparison of the effects of low-level laser therapy and ozone therapy on bone healing. J Craniofac Surg. 2015;26(5):e396-e400. Available from: https://doi.org/10.1097/SCS.0000000000001871 DOI: https://doi.org/10.1097/SCS.0000000000001871 DOI: https://doi.org/10.1097/SCS.0000000000001871

9. Kazancioglu HO, Ezirganli S, Aydin MS. Effects of laser and ozone therapies on bone healing in the calvarial defects. J Craniofac Surg. 2013;24(6):2141-2146. Available from: https://doi.org/10.1097/scs.0b013e3182a244ae DOI: https://doi.org/10.1097/SCS.0b013e3182a244ae DOI: https://doi.org/10.1097/SCS.0b013e3182a244ae

10. Yucesoy T, Kutuk N, Canpolat DG, Alkan A. Comparison of ozone and photobiomodulation therapies on mental nerve injury in rats. J Oral Maxillofac Surg. 2017;75(11):2323-2332. Available from: https://doi.org/10.1016/j.joms.2017.04.016 DOI: https://doi.org/10.1016/j.joms.2017.04.016 DOI: https://doi.org/10.1016/j.joms.2017.04.016

11. Yuca Y, Yucesoy T, Tok OE, Alkan A. The efficiency of ozone therapy and low-level laser therapy in rat facial nerve injury. J Craniomaxillofac Surg. 2020;48(3):308-314. Available from: https://doi.org/10.1016/j.jcms.2020.01.017 DOI: https://doi.org/10.1016/j.jcms.2020.01.017 DOI: https://doi.org/10.1016/j.jcms.2020.01.017

12. Bayer S, Kazancioglu HO, Acar AH, Demirtas N, Kandas NO. Comparison of laser and ozone treatments on oral mucositis in an experimental model. Lasers Med Sci. 2017;32(3):673-677. Available from: https://doi.org/10.1007/s10103-017-2166-1 DOI: https://doi.org/10.1007/s10103-017-2166-1 DOI: https://doi.org/10.1007/s10103-017-2166-1

13. Eckelman WC, Kilbourn MR, Joyal JL, Labiris R, Valliant JF. Justifying the number of animals for each experiment. Nucl Med Biol. 2007;34(3):229-232. Available from: https://doi.org/10.1016/j.nucmedbio.2007.01.005 DOI: https://doi.org/10.1016/j.nucmedbio.2007.01.005 DOI: https://doi.org/10.1016/j.nucmedbio.2007.01.005

14. Scheibe PO. Number of samples — hypothesis testing. Nucl Med Biol. 2008;35(1):3-9. Available from: https://doi.org/10.1016/j.nucmedbio.2007.10.006 DOI: https://doi.org/10.1016/j.nucmedbio.2007.10.006 DOI: https://doi.org/10.1016/j.nucmedbio.2007.10.006

15. Damy SB, Camargo RS, Chammas R, de Figueiredo LFP. Aspectos fundamentais da experimentação animal: aplicações em cirurgia experimental. Rev Assoc Med Bras. 2010;56(1):103-111. Available from: https://doi.org/10.1590/S0104-42302010000100024 DOI: https://doi.org/10.1590/S0104-42302010000100024 DOI: https://doi.org/10.1590/S0104-42302010000100024

16. Medrado AR, Pugliese LS, Reis SRA, Andrade ZA. Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts. Lasers Surg Med. 2003;32(3):239-244. Available from: https://doi.org/10.1002/lsm.10126 DOI: https://doi.org/10.1002/lsm.10126 DOI: https://doi.org/10.1002/lsm.10126

17. Braitenbach BPF, Cerqueira CBS, Lima SS, Hegouet IC, Moreno BCL, Medrado ARAP. Effects of photobiomodulation on adipocytic infiltration in sites of skin healing: in vivo experimental study. Lasers Med Sci. 2025;40(1):153. Available from: https://doi.org/10.1007/s10103-025-04410-1 DOI: https://doi.org/10.1007/s10103-025-04410-1 DOI: https://doi.org/10.1007/s10103-025-04410-1

18. Alvarenga MOP, Bittencourt LO, Mendes PFS, Ribeiro JT, Lameira OA, Monteiro MC, et al. Safety and effectiveness of copaiba oleoresin (C. reticulata Ducke) on inflammation and tissue repair of oral wounds in rats. Int J Mol Sci. 2020;21(10):3568. Available from: https://doi.org/10.3390/ijms21103568 DOI: https://doi.org/10.3390/ijms21103568 DOI: https://doi.org/10.3390/ijms21103568

19. Cañedo-Dorantes L, Cañedo-Ayala M. Skin Acute Wound Healing: A Comprehensive Review. Biomed Res Int. 2019;2019:3708260. Available from: https://doi.org/10.1155/2019/3706315 DOI: https://doi.org/10.1155/2019/3706315 DOI: https://doi.org/10.1155/2019/3706315

20. Sampaio LAS, Costa JS, Freire TFC, Reis SRA, Deiró TCBJ, Medrado ARAP. Influence of protein malnutrition on cutaneous wound healing in rats. Rev Nutr. 2018;31(5):433-442. Available from: https://doi.org/10.1590/1678-98652018000500001 DOI: https://doi.org/10.1590/1678-98652018000500001 DOI: https://doi.org/10.1590/1678-98652018000500001

21. Fortuna T, Gonzalez AC, Sá MF, Andrade ZA, Reis SRA, Medrado ARAP. Effect of 670 nm laser photobiomodulation on vascular density and fibroplasia in late stages of tissue repair. Int Wound J. 2018;15(2):274-282. Available from: https://doi.org/10.1111/iwj.12861 DOI: https://doi.org/10.1111/iwj.12861 DOI: https://doi.org/10.1111/iwj.12861

22. Hegouet IC, Lima SS, Medrado ARAP. Efeitos da ozonioterapia sobre as fibras colágenas e elásticas no reparo cutâneo: um estudo histomorfométrico em ratos. Rev Ciênc Méd Biol. 2024;23(2):242-248. Available from: https://doi.org/10.9771/cmbio.v23i2.64117 DOI: https://doi.org/10.9771/cmbio.v23i2.64117 DOI: https://doi.org/10.9771/cmbio.v23i2.64117

23. Pourhashemi E, Amini A, Ahmadi H, Ahrabi B, Mostafavinia A, Omidi H, et al. Photobiomodulation and conditioned medium of adipose-derived stem cells for enhancing wound healing in rats with diabetes: an investigation on the proliferation phase. Lasers Med Sci. 2024;39(1):46. Available from: https://doi.org/10.1007/s10103-024-03974-8 DOI: https://doi.org/10.1007/s10103-024-03974-8 DOI: https://doi.org/10.1007/s10103-024-03974-8

24. Mostafavinia A, Amini A, Sajadi E, Ahmadi H, Rezaei F, Ghoreishi SK, et al. Photobiomodulation therapy was more effective than photobiomodulation plus arginine on accelerating wound healing in an animal model of delayed healing wound. Lasers Med Sci. 2022;37(1):403-415. Available from: https://doi.org/10.1007/s10103-021-03271-8 DOI: https://doi.org/10.1007/s10103-021-03271-8 DOI: https://doi.org/10.1007/s10103-021-03271-8

25. Kim HS, Noh SU, Han YW, Kim KM, Kang H, Kim HO, et al. Therapeutic effects of topical application of ozone on acute cutaneous wound healing. J Korean Med Sci. 2009;24(3):368-374. Available from: https://doi.org/10.3346/jkms.2009.24.3.368 DOI: https://doi.org/10.3346/jkms.2009.24.3.368 DOI: https://doi.org/10.3346/jkms.2009.24.3.368

26. Pchepiorka R, Moreira MS, Lascane NADS, Catalani LH, Allegrini S Jr, de Lima NB, et al. Effect of ozone therapy on wound healing in the buccal mucosa of rats. Arch Oral Biol. 2020;119:104889. Available from: https://doi.org/10.1016/j.archoralbio.2020.104889 DOI: https://doi.org/10.1016/j.archoralbio.2020.104889 DOI: https://doi.org/10.1016/j.archoralbio.2020.104889

27. Cardoso JM, Ervolino E, Miyasawa EM, Theodoro LH, Padovan LEM, Pereira EL, et al. Unveiling the therapeutic potential of systemic ozone on skin wound repair: clinical, histological, and immunohistochemical study in rats. Biomed Res Int. 2024;2024:6623114. Available from: https://doi.org/10.1155/2024/6623114 DOI: https://doi.org/10.1155/2024/6623114 DOI: https://doi.org/10.1155/2024/6623114

28. Soares CD, Morais TML, Araújo RMFG, Meyer PF, Oliveira EAF, Silva RMV, et al. Effects of subcutaneous injection of ozone during wound healing in rats. Growth Factors. 2019;37(1-2):95-103. Available from: https://doi.org/10.1080/08977194.2019.1643339 DOI: https://doi.org/10.1080/08977194.2019.1643339 DOI: https://doi.org/10.1080/08977194.2019.1643339

29. Acikan I, Sayeste E, Bozoglan A, Artas G, Isayev A, Kirtay M, et al. Evaluation of the effects of topical application of chlorhexidine, ozone, and metronidazole on palatal wound healing: a histopathological study. J Craniofac Surg. 2022;33(6):1929-1933. Available from: https://doi.org/10.1097/scs.0000000000008390 DOI: https://doi.org/10.1097/SCS.0000000000008390 DOI: https://doi.org/10.1097/SCS.0000000000008390

30. Xiao W, Tang H, Wu M, Liao Y, Li K, Li L, et al. Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway. Biosci Rep. 2017;37(6):BSR20170658. Available from: https://doi.org/10.1042/bsr20170658 DOI: https://doi.org/10.1042/BSR20170658 DOI: https://doi.org/10.1042/BSR20170658

31. Sathwik M, Komarraju S, Sathyanath D, Muralidharan S. Technical considerations of ozonated oils in medical applications: a narrative review. Cureus. 2025;17(4):e83185. Available from: https://doi.org/10.7759/cureus.83185 DOI: https://doi.org/10.7759/cureus.83185 DOI: https://doi.org/10.7759/cureus.83185

32. Rafiei Y, Ghamsari SM, Sasani F, Ezzaty A, Golchin D, Akbari AM, et al. Evaluation of the healing effects of different methods of using ozone in third-degree skin burns in the rat experimental model. Iran J Vet Surg. 2025;20(1):47-54. Available from: https://doi.org/10.30500/ivsa.2024.453505.1402 DOI: https://doi.org/10.30500/ivsa.2024.453505.1402

33. Liu L, Zeng L, Gao L, Zeng J, Lu J. Ozone therapy for skin diseases: cellular and molecular mechanisms. Int Wound J. 2023;20(6):2376-2385. Available from: https://doi.org/10.1111/iwj.14060 DOI: https://doi.org/10.1111/iwj.14060 DOI: https://doi.org/10.1111/iwj.14060

34. Krkl C, Yiğit MV, Özercan İH, Aygen E, Gültürk B, Artaş G. The effect of ozonated olive oil on neovascularization in an experimental skin flap model. Adv Skin Wound Care. 2016;29(7):322-327. Available from: https://doi.org/10.1097/01.asw.0000484172.04260.46 DOI: https://doi.org/10.1097/01.ASW.0000484172.04260.46 DOI: https://doi.org/10.1097/01.ASW.0000484172.04260.46

35. Zhu M, Cao L, Melino S, Candi E, Wang Y, Shao C, et al. Orchestration of mesenchymal stem/stromal cells and inflammation during wound healing. Stem Cells Transl Med. 2023;12(9):576-587. Available from: https://doi.org/10.1093/stcltm/szad043 DOI: https://doi.org/10.1093/stcltm/szad043 DOI: https://doi.org/10.1093/stcltm/szad043

36. Veith AP, Henderson K, Spencer A, Sligar AD, Baker AB. Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev. 2019;146:97-125. Available from: https://doi.org/10.1016/j.addr.2018.09.010 DOI: https://doi.org/10.1016/j.addr.2018.09.010 DOI: https://doi.org/10.1016/j.addr.2018.09.010

37. Castro TNS, Martignago CCS, Assis L, de Alexandria FED, Rocha JCT, Parizotto NA, et al. Effects of photobiomodulation therapy in the integration of skin graft in rats. Lasers Med Sci. 2020;35(4):939-947. Available from: https://doi.org/10.1007/s10103-019-02909-y DOI: https://doi.org/10.1007/s10103-019-02909-y DOI: https://doi.org/10.1007/s10103-019-02909-y

38. de Oliveira LP, Chagas AL, de Souza TR, Araújo IR, de Menezes LB, Miguel MP, et al. Low-power laser in increasing doses improve wound healing process in rats. Lasers Med Sci. 2023;38(1):60. Available from: https://doi.org/10.1007/s10103-023-03716-2 DOI: https://doi.org/10.1007/s10103-023-03716-2 DOI: https://doi.org/10.1007/s10103-023-03716-2

39. Andrade TOS, Dantas BL, Cerqueira CBS, Badaró P, Marchionni AMT, Medrado ARAP. Comparative study of the effectiveness of ozone therapy and laser photobiomodulation upon experimental wound repair: systematic review. Res Soc Dev. 2022;11(5):e58911528650. Available from: https://doi.org/10.33448/rsd-v11i5.28650 DOI: https://doi.org/10.33448/rsd-v11i5.28650 DOI: https://doi.org/10.33448/rsd-v11i5.28650

40. Waasdorp M, Krom BP, Bikker FJ, van Zuijlen PPM, Niessen FB, Gibbs S. The bigger picture: why oral mucosa heals better than skin. Biomolecules. 2021;11(8):1165. Available from: https://doi.org/10.3390/biom11081165 DOI: https://doi.org/10.3390/biom11081165 DOI: https://doi.org/10.3390/biom11081165

41. Moreira SH, Pazzini JM, Álvarez JLG, Cassino PC, Bustamante CC, Bernardes FJL, et al. Evaluation of angiogenesis, inflammation, and healing on irradiated skin graft with low-level laser therapy in rats (Rattus norvegicus albinus Wistar). Lasers Med Sci. 2020;35(5):1103-1109. Available from: https://doi.org/10.1007/s10103-019-02917-y DOI: https://doi.org/10.1007/s10103-019-02917-y DOI: https://doi.org/10.1007/s10103-019-02917-y

42. Calisto FC, Calisto SL, Souza AP, França CM, Ferreira AP, Moreira MB. Use of low-power laser to assist the healing of traumatic wounds in rats. Acta Cir Bras. 2015;30(3):204-208. Available from: https://doi.org/10.1590/s0102-865020150030000007 DOI: https://doi.org/10.1590/S0102-865020150030000007 DOI: https://doi.org/10.1590/S0102-865020150030000007

43. Hidayat AT, Arifin MT, Nur M, Muniroh M, Susilaningsih N. Ozonated Aloevera oil effectively increased the number of fibroblasts and collagen thickening in the healing response of full-thickness skin defects. Int J Inflam. 2021;2021:6654343. Available from: https://doi.org/10.1155/2021/6654343 DOI: https://doi.org/10.1155/2021/6654343 DOI: https://doi.org/10.1155/2021/6654343

Como Citar

Quadros Lima, F., Marchionni, A. M. ., Paim de Figueiredo Braitenbach, B. ., Carvalho Lopez Moreno, B. ., Souza Lima, S. ., Barreto Cerqueira, C. ., & Medrado, A. R. A. P. (2026). AVALIAÇÃO HISTOLÓGICA DE FERIDAS CUTÂNEAS DE RATOS SUBMETIDAS À FOTOBIOMODULAÇÃO LASER E OZONIOTERAPIA. RECIMA21 - Revista Científica Multidisciplinar - ISSN 2675-6218, 7(3), e737325. https://doi.org/10.47820/recima21.v7i3.7325