Efetividade do gel liberador de oxigênio ativo associado à terapia fotodinâmica antimicrobiana como tratamento preventivo para a osteonecrose dos maxilares induzida por medicamentos
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Data
2023-01-12
Autores
Franciscon, João Paulo Soares [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A osteonecrose dos maxilares associada à terapia medicamentosa (ONMM) é uma condição patológica de difícil tratamento. Sendo assim, a conduta ideal é o estabelecimento de estratégias que visem prevenir sua ocorrência. A terapia tópica com gel liberador de oxigênio ativo (TTGLOA) e a terapia fotodinâmica antimicrobiana (aPDT) apresentam concomitantemente atividade antimicrobiana e ação biomodulatória, o que as colocam como potenciais estratégias preventivas para a ONMM. O objetivo do presente estudo foi avaliar a efetividade do TTGLOA em associação com aPDT no processo de reparo alveolar em ratas senescentes tratadas com dose oncológica de zoledronato, e analisar o seu potencial na prevenção da ocorrência da ONMM. Vinte e oito ratas senescentes foram divididas em quatro grupos experimentais: NTL, TTGLOA, aPDT e TTGLOA+aPDT. No dia 0 foi realizada a instalação de uma ligadura ao redor do primeiro molar inferior do lado esquerdo para indução da periodontite experimental. Do dia 1 ao dia 50 as ratas receberam, a cada 3 dias, 0,45 ml de zoledronato (100 µg/Kg), pela via intraperitoneal. Após 3 semanas de tratamento com zoledronato foi efetuada a extração do primeiro molar inferior do lado esquerdo. No grupo NTL (n=7) não foi efetuado nenhum tratamento local. No grupo TTGLOA (n= 7) e no grupo aPDT (n=7), os alvéolos foram submetidos a três sessões de TTGLOA e aPDT, respectivamente. No grupo TTGLOA+aPDT (n=7) os alvéolos foram submetidos a três sessões de TTGLOA seguida de aPDT. Os tratamentos locais foram efetuados aos 0, 2 e 4 após exodontia. As eutanásias foram realizadas aos 28 dias pós exodontia. As hemimandíbulas foram devidamente processadas para permitir: análise histológica, análise histométrica da porcentagem de tecido ósseo neoformado (TONF) e de tecido ósseo não vital (TONV) e análise imunoistoquímica (BMP2/4, proteína morfogenética óssea 2/4 e; OCN, osteocalcina). O grupo NTL apresentou grande comprometimento do processo de reparação tecidual. Os grupos TTGLOA, aPDT e TTGLOA+aPDT apresentaram um processo de reparação tecidual favorável do sítio de extração dental. No grupo NTL a porcentagem de TONF foi menor, enquanto que, a porcentagem de TONV foi maior, que nos demais grupos. O grupo TTGLOA apresentou menor porcentagem de TONF e maior porcentagem de TONV quando comparado com os grupos aPDT e TTGLOA+aPDT. No grupo TTGLOA+aPDT a porcentagem de TONF foi maior que no grupo aPDT. O grupo TTGLOA+aPDT apresentou o maior padrão de imunomarcação para BMP2/4 e para OCN. A TTGLOA, aPDT e TTGLOA+aPDT foram capazes de evitar a ocorrência da ONMM pós exodontia com diferentes níveis de efetividade. Como monoterapia, a aPDT foi superior a TTGLOA, todavia, a maior efetividade foi obtida com o emprego da TTGLOA+aPDT.
The medication-related osteonecrosis of the jaws (MRONJ) is a pathological condition that is difficult to treat. Therefore, the ideal conduct is establishment of strategies aimed at preventing its ocurrence. Topical therapy with active oxygen-releasing gel (TTAORG) and the antimicrobial photodynamic therapy (aPDT) have antimicrobial activity and biomodulation action, which makes them potencial preventive strategies to MRONJ. The aim of this study was to evaluate the effectiveness of TTAORG in association with aPDT in the alveolar repair in senescent female rats treated with oncological dose of zoledronate and to analyze its potention in preventing the occurence of MRONJ. Twenty-eight senescent female rats were divided in four experimental groups: NLT, TTAORG, aPDT, TTAORG+aPDT. On 0 day a ligature was installed around the mandibular first molar on the left side to induce experimental periodontitis. From day 1 to 50, the rats received, every three days, 0.45 ml of zoledronate (100 μg/Kg), intraperitoneally. After three weeks of treatment with zoledronate, the mandibular first molar on the left side was extracted. In the NLT group (n=7) no local treatment was performed. In the TTAORG group (n=7) and in the aPDT group (n=7) the socket was submitted to three sessions of TTAORG and aPDT, respectively. In the TTAORG+aPDT group (n=7) the socket was submitted to three sessions of TTAORG followed by aPDT. Local treatments were performed at 0, 2 and 4 days after dental extraction. Euthanasia was performed 28 days after dental extraction. The hemimandibles were processed to allow: histological analysis, histometrical analysis of the percentage of newly formed bone tissue (NFBT) and non-vital bone tissue (NVBT) and immunohistochemical analysis (BMP2/4, morfogenetic bone protein 2/4 and; OCN, osteocalcin). The NLT group showed a great impairment of tissue repair process. The TTAORG, aPDT and TTAORG+aPDT groups showed a favorable tissue repair at the dental extraction site. In the NLT group, the percentage of NFBT was lower, while the percentage of NVBT was higher than the other groups. The TTAORG group showed lower percentage of NFBT and a higher percentage of NVBT when compared with the aPDT and TTAORG+aPDT groups. In the TTAORG+aPDT group the percentage of NFBT was higher than aPDT group. The TTAORG+aPDT group showed the highest pattern of immunolabeling for BMP2/4 and OCN. TTAORG, aPDT and TTAORG+aPDT were able to avoid the occurence of MRONJ after dental extraction with differents levels of effectiveness. As a monotherapy, aPDT was better than TTAORG, but, the greatest effectiveness was obtained with the use of TTAORG+aPDT.
The medication-related osteonecrosis of the jaws (MRONJ) is a pathological condition that is difficult to treat. Therefore, the ideal conduct is establishment of strategies aimed at preventing its ocurrence. Topical therapy with active oxygen-releasing gel (TTAORG) and the antimicrobial photodynamic therapy (aPDT) have antimicrobial activity and biomodulation action, which makes them potencial preventive strategies to MRONJ. The aim of this study was to evaluate the effectiveness of TTAORG in association with aPDT in the alveolar repair in senescent female rats treated with oncological dose of zoledronate and to analyze its potention in preventing the occurence of MRONJ. Twenty-eight senescent female rats were divided in four experimental groups: NLT, TTAORG, aPDT, TTAORG+aPDT. On 0 day a ligature was installed around the mandibular first molar on the left side to induce experimental periodontitis. From day 1 to 50, the rats received, every three days, 0.45 ml of zoledronate (100 μg/Kg), intraperitoneally. After three weeks of treatment with zoledronate, the mandibular first molar on the left side was extracted. In the NLT group (n=7) no local treatment was performed. In the TTAORG group (n=7) and in the aPDT group (n=7) the socket was submitted to three sessions of TTAORG and aPDT, respectively. In the TTAORG+aPDT group (n=7) the socket was submitted to three sessions of TTAORG followed by aPDT. Local treatments were performed at 0, 2 and 4 days after dental extraction. Euthanasia was performed 28 days after dental extraction. The hemimandibles were processed to allow: histological analysis, histometrical analysis of the percentage of newly formed bone tissue (NFBT) and non-vital bone tissue (NVBT) and immunohistochemical analysis (BMP2/4, morfogenetic bone protein 2/4 and; OCN, osteocalcin). The NLT group showed a great impairment of tissue repair process. The TTAORG, aPDT and TTAORG+aPDT groups showed a favorable tissue repair at the dental extraction site. In the NLT group, the percentage of NFBT was lower, while the percentage of NVBT was higher than the other groups. The TTAORG group showed lower percentage of NFBT and a higher percentage of NVBT when compared with the aPDT and TTAORG+aPDT groups. In the TTAORG+aPDT group the percentage of NFBT was higher than aPDT group. The TTAORG+aPDT group showed the highest pattern of immunolabeling for BMP2/4 and OCN. TTAORG, aPDT and TTAORG+aPDT were able to avoid the occurence of MRONJ after dental extraction with differents levels of effectiveness. As a monotherapy, aPDT was better than TTAORG, but, the greatest effectiveness was obtained with the use of TTAORG+aPDT.
Descrição
Palavras-chave
Osteonecrose, Espécies reativas de oxigênio, Fotoquimioterapia, Ácido Zoledrônico, Osteonecrosis