Avaliação do emprego da curcumina associada ao diodo emissor de luz durante o reparo alveolar em ratas com alto risco para a osteonecrose dos maxilares
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2022-02-25
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Universidade Estadual Paulista (Unesp)
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A osteonecrose dos maxilares associada à terapia medicamentosa (ONMM) é um grave efeito adverso que pode ser ocasionado pelo uso de medicamentos com ação antirreabsortiva. Essa é uma condição patológica de difícil tratamento, em sendo assim, a prevenção seria a estratégia ideal. Estudos mostram que a curcumina (CUR) apresenta ação anti-inflamatória, efeito antimicrobiano e alta capacidade para estimular a reparação tecidual, além disso, pode ser usada como fotossensibilizador na terapia fotodinâmica antimicrobiana (aPDT), o que a coloca como uma potencial estratégia terapêutica preventiva para a ONMM. O objetivo do presente estudo foi avaliar o efeito da aPDT, empregando CUR e diodo emissor de luz (LED) azul, no sítio de extração dental de ratas que apresentavam alto risco para a ONMM. Cinquenta e seis ratas senescentes foram distribuídas em oito grupos experimentais: VEI; VEI-LED; VEICUR; VEI-aPDT; ZOL; ZOL-LED; ZOL-CUR; ZOL-aPDT. O plano de tratamento medicamentoso teve duração de 7 semanas. As ratas dos grupos VEI; VEI-LED; VEI-CUR; VEI-aPDT receberam 0,45 ml de veículo (cloreto de sódio 0,9%). As ratas dos grupos ZOL; ZOL-LED; ZOL-CUR; ZOL-aPDT receberam o veículo acrescido de 100 μg/Kg de zoledronato. O veículo e o zoledronato foram administrados a cada 72 horas pela via intraperitoneal. Decorridas 3 semanas de tratamento todas as ratas foram submetidas à exodontia do primeiro molar inferior. Nos grupos VEI-LED e ZOL-LED foram efetuadas 4 sessões de irradiação com LED. Nos grupos VEI-CUR e ZOL-CUR foram efetuadas 4 sessões de deposição de CUR. Nos grupos VEI-aPDT e ZOL-aPDT foram efetuadas 4 sessões de aPDT empregando a CUR e o LED. Os tratamentos locais foram efetuados aos 0, 2, 4 e 6 dias pós-operatórios. Decorridos 28 dias pós-operatórios foi realizada a eutanásia. As hemimandíbulas foram devidamente processadas para que se pudesse ser efetuado no sítio de extração dental: 1) análise clínica; 2) análise histológica da reparação tecidual; 3) análise histométrica da porcentagem de Tecido Ósseo Neoformado (TONF) e Tecido Ósseo Não Vital (TONV) e; 4) análise imunoistoquímica para os marcadores VEGF, TGFβ1, BMP2/4 e OCN. Os grupos ZOL e ZOL-LED apresentaram severo comprometimento do processo de reparo alveolar, menor porcentagem de TONF, maior porcentagem de TONV e baixo padrão de imunomarcação para VEGF, TGFβ1, BMP2/4 e OCN. Quando comparados com esses grupos, os grupos ZOL-CUR e ZOL-aPDT apresentaram um curso do processo de reparação tecidual favorável, maior porcentagem de TONF, menor porcentagem de TONV e padrão de imunomarcação de moderado a alto para VEGF, TGFβ1, BMP2/4 e OCN. Os grupos ZOL-CUR e ZOL-aPDT mostraram muita similaridade com o grupo VEI na maioria dos parâmetros avaliados neste estudo. Quando ZOL-CUR e ZOL-aPDT são comparados entre si, este último se mostrou superior em alguns dos parâmetros. Conclui-se que a curcumina exerce efeitos positivos sobre o processo de reparo alveolar em ratas senescentes tratadas com altas doses de zoledronato. Os efeitos benéficos sobre a reparação tecidual são potencializados quando a curcumina é associada à irradiação com LED azul, ou seja, na aPDT. O uso da curcumina, irradiada ou não com LED azul, evitou a ocorrência ONMM.
Osteonecrosis of the jaws associated with drug therapy (ONMM) is a serious adverse effect that can be caused by the use of drugs with antiresorptive action. This is a pathological condition that is difficult to treat, so prevention would be the ideal strategy. Studies show that curcumin (CUR) has anti-inflammatory action, antimicrobial effect and high capacity to stimulate tissue repair, in addition, it can be used as a photosensitizer in antimicrobial photodynamic therapy (aPDT), which makes it a potential therapeutic strategy. preventive action for the ONMM. The aim of the present study was to evaluate the effect of aPDT, using CUR and blue light-emitting diode (LED), at the dental extraction site of rats at high risk for NMM. Fifty-six senescent rats were divided into eight experimental groups: VEI; VEI-LED; VEI-CUR; VEI-aPDT; ZOL; ZOL-LED; ZOL-CUR; ZOL-aPDT. The drug treatment plan lasted 7 weeks. The rats of the VEI groups; VEI-LED; VEI-CUR; VEI-aPDT received 0.45 ml of vehicle (0.9% sodium chloride). The rats of the ZOL groups; ZOL-LED; ZOL-CUR; ZOLaPDT received the vehicle plus 100 μg/Kg of zoledronate. The vehicle and zoledronate were administered intraperitoneally every 72 hours. After 3 weeks of treatment, all rats underwent extraction of the lower first molar. In the VEI-LED and ZOL-LED groups, 4 sessions of LED irradiation were performed. In the VEI-CUR and ZOL-CUR groups, 4 CUR deposition sessions were performed. In the VEI-aPDT and ZOL-aPDT groups, 4 aPDT sessions were performed using CUR and LED. Local treatments were performed at 0, 2, 4 and 6 postoperative days. After 28 postoperative days, euthanasia was performed. The hemimandibles were properly processed so that the following could be performed at the tooth extraction site: 1) clinical analysis; 2) histological analysis of tissue repair; 3) histometric analysis of the percentage of Neoformed Bone Tissue (TONF) and Non-Vital Bone Tissue (TONV) and; 4) immunohistochemical analysis for VEGF, TGFβ1, BMP2/4 and OCN markers. The ZOL and ZOL-LED groups showed severe impairment of the alveolar repair process, lower percentage of TONF, higher percentage of TONV and low immunostaining pattern for VEGF, TGFβ1, BMP2/4 and OCN. When compared with these groups, the ZOL-CUR and ZOL-aPDT groups showed a favorable course of tissue repair, higher percentage of TONF, lower percentage of TONV and moderate to high immunostaining pattern for VEGF, TGFβ1, BMP2/4 and OCN. The ZOL-CUR and ZOL-aPDT groups showed a lot of similarity with the VEI group in most of the parameters evaluated in this study. When ZOL-CUR and ZOL-aPDT are compared, the latter proved to be superior in some of the parameters. It is concluded that curcumin exerts positive effects on the alveolar repair process in senescent rats treated with high doses of zoledronate. The beneficial effects on tissue repair are potentiated when curcumin is associated with blue LED irradiation, that is, in aPDT. The use of curcumin, whether or not irradiated with blue LED, prevented the occurrence of ONMM.
Osteonecrosis of the jaws associated with drug therapy (ONMM) is a serious adverse effect that can be caused by the use of drugs with antiresorptive action. This is a pathological condition that is difficult to treat, so prevention would be the ideal strategy. Studies show that curcumin (CUR) has anti-inflammatory action, antimicrobial effect and high capacity to stimulate tissue repair, in addition, it can be used as a photosensitizer in antimicrobial photodynamic therapy (aPDT), which makes it a potential therapeutic strategy. preventive action for the ONMM. The aim of the present study was to evaluate the effect of aPDT, using CUR and blue light-emitting diode (LED), at the dental extraction site of rats at high risk for NMM. Fifty-six senescent rats were divided into eight experimental groups: VEI; VEI-LED; VEI-CUR; VEI-aPDT; ZOL; ZOL-LED; ZOL-CUR; ZOL-aPDT. The drug treatment plan lasted 7 weeks. The rats of the VEI groups; VEI-LED; VEI-CUR; VEI-aPDT received 0.45 ml of vehicle (0.9% sodium chloride). The rats of the ZOL groups; ZOL-LED; ZOL-CUR; ZOLaPDT received the vehicle plus 100 μg/Kg of zoledronate. The vehicle and zoledronate were administered intraperitoneally every 72 hours. After 3 weeks of treatment, all rats underwent extraction of the lower first molar. In the VEI-LED and ZOL-LED groups, 4 sessions of LED irradiation were performed. In the VEI-CUR and ZOL-CUR groups, 4 CUR deposition sessions were performed. In the VEI-aPDT and ZOL-aPDT groups, 4 aPDT sessions were performed using CUR and LED. Local treatments were performed at 0, 2, 4 and 6 postoperative days. After 28 postoperative days, euthanasia was performed. The hemimandibles were properly processed so that the following could be performed at the tooth extraction site: 1) clinical analysis; 2) histological analysis of tissue repair; 3) histometric analysis of the percentage of Neoformed Bone Tissue (TONF) and Non-Vital Bone Tissue (TONV) and; 4) immunohistochemical analysis for VEGF, TGFβ1, BMP2/4 and OCN markers. The ZOL and ZOL-LED groups showed severe impairment of the alveolar repair process, lower percentage of TONF, higher percentage of TONV and low immunostaining pattern for VEGF, TGFβ1, BMP2/4 and OCN. When compared with these groups, the ZOL-CUR and ZOL-aPDT groups showed a favorable course of tissue repair, higher percentage of TONF, lower percentage of TONV and moderate to high immunostaining pattern for VEGF, TGFβ1, BMP2/4 and OCN. The ZOL-CUR and ZOL-aPDT groups showed a lot of similarity with the VEI group in most of the parameters evaluated in this study. When ZOL-CUR and ZOL-aPDT are compared, the latter proved to be superior in some of the parameters. It is concluded that curcumin exerts positive effects on the alveolar repair process in senescent rats treated with high doses of zoledronate. The beneficial effects on tissue repair are potentiated when curcumin is associated with blue LED irradiation, that is, in aPDT. The use of curcumin, whether or not irradiated with blue LED, prevented the occurrence of ONMM.
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Palavras-chave
Zoledronato, Osteonecrose, Terapia fotodinâmica antimicrobiana, Curcumina, Zoledronate, Osteonecrosis, Antimicrobial photodynamic therapy, Curcumin