Revista de Odontologia da UNESP
Revista de Odontologia da UNESP
Original Article

Effect of systemic ozone therapy as a biomodulator of tissue regeneration and inflammatory response in rats

Efeito da terapia sistêmica de ozônio como um biomodulador da regeneração tecidual e da resposta inflamatória em ratos

Juliana Rico PIRES; Alexandre Melo KARAM; Valdir Gouveia GARCIA; Fernando Salimon RIBEIRO; Ana Emilia Farias PONTES; Cleverton Roberto de ANDRADE; Elizangela Cruvinel ZUZA

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Abstract: Introduction: Among the therapeutic effects of ozone therapy, improvement in cell metabolism and peripheral tissue oxygenation have been highlighted.

Objective: to evaluate the systemic effect of bio-oxidative therapy with ozone gas on wound healing.

Material and method: Tissue lesions with a circumference of 1.0 cm were induced in the skin on the back of 24 male Wistar rats. The animals were randomly divided into two groups: 1) Group C (control; n=12): with simulation of the application of ozone gas via the rectum and, 2) Group O3 (test; n=12): with application of ozone gas by means of rectal insufflation at a concentration of 50 µg/mL. The animals were euthanized at seven and 15 days, and samples were removed, fixed in formalin, and submitted to macroscopic, histological, and histometric analyses.

Result: The animals in the O3 group presented mixed inflammation at seven days, which translated into an absence of inflammation at 15 days. The C group exhibited acute inflammation on the 7th day, translating to chronic inflammation, which significantly increased from the 7th to the 15th day. The findings showed that the O3 group presented greater wound contraction (P<0.05) and a greater degree of neovascularization on the 7th day (P<0.05) when compared to group C. On the 15th day, both groups (O3 and C) showed complete re-epithelialization, however, the O3 group demonstrated complete muscle regeneration.

Conclusion: The systemic ozone therapy had a biomodulatory effect, reducing the characteristics of acute inflammation and increasing tissue repair and regeneration in rat skin.


Ozone, wound healing, inflammation, rats


Resumo: Introdução: Dentre os efeitos terapêuticos da ozonioterapia, destacam-se a melhora do metabolismo celular e da oxigenação dos tecidos periféricos.

Objetivo: avaliar o efeito sistêmico da terapia bio-oxidativa com gás ozônio na cicatrização de feridas.

Material e método: Lesões teciduais com circunferência de 1,0 cm foram induzidas na pele do dorso de 24 ratos Wistar machos. Os animais foram divididos aleatoriamente em dois grupos: 1) Grupo C (controle; n = 12): com simulação da aplicação de gás ozônio pelo reto e, 2) Grupo O3 (teste; n = 12): com aplicação de gás ozônio por meio de insuflação retal na concentração de 50 µg / mL. Os animais foram sacrificados com sete e 15 dias, e as amostras foram retiradas, fixadas em formalina e submetidas às análises macroscópica, histológica e histométrica.

Resultado: Os animais do grupo O3 apresentaram inflamação mista aos sete dias, que se traduziu em ausência de inflamação aos 15 dias. O grupo C apresentou inflamação aguda no 7º dia, traduzindo-se em inflamação crônica, que aumentou significativamente do 7º para o 15º dia. Os achados mostraram que o grupo O3 apresentou maior contração da ferida (P <0,05) e maior grau de neovascularização no 7º dia (P <0,05) quando comparado ao grupo C. No 15º dia, ambos os grupos (O3 e C) apresentaram completa reepitelização, entretanto, o grupo O3 demonstrou completa regeneração muscular.

Conclusão: A ozonioterapia sistêmica teve efeito biomodulador, reduzindo as características de inflamação aguda e aumentando a reparação e regeneração tecidual na pele de ratos.


Ozônio, cicatrização, inflamação, ratos


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