Efeito do tratamento local com nanoemulsão de própolis verde no sítio de extração dental de ratas com os principais fatores de risco para osteonecrose dos maxilares associada à terapia medicamentosa
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Data
2022-05-31
Autores
Freire, Jéssica De Oliveira Alvarenga [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Os bisfosfonatos são medicamentos antirreabsortivos empregados para tratamento de doenças/lesões osteolíticas, cujo uso tem como efeito adverso a osteonecrose dos maxilares associada à terapia medicamentosa (ONM-M). O estabelecimento de terapias preventivas efetivas e seguras para a ONM-M é importante, pois seu tratamento pode ser pouco resolutivo. A própolis é um material resinoso produzido por abelhas que apresenta ações antimicrobiana, bioestimulatória, imunomodulatória, anti-inflamatória e antioxidante. Seu uso sob forma de nanoemulsão, com objetivo de melhora de solubilidade, absorção e efeitos, pode se constituir em uma promissora estratégia terapêutica preventiva para a ONM-M. O objetivo do presente estudo foi avaliar o efeito da administração local de nanoemulsão de própolis verde no sítio de extração dental de ratas com os principais fatores de risco da ONM-M. Sessenta ratas foram divididas em seis grupos experimentais: VEI, VEI-PRO1, VEI-PRO2, ZOL, ZOL-PRO1 e ZOL-PRO2. Grupos VEI foram tratados com veículo (solução de cloreto de sódio 0,9%) e grupos ZOL com zoledronato (100μg/kg) durante todo período experimental (7 semanas). Em todos os animais, o primeiro molar inferior esquerdo foi submetido à periodontite induzida por ligadura e extraído. Os grupos VEI e ZOL não receberam nenhum tratamento local após a exodontia. Nos grupos VEI-PRO1 e ZOL-PRO1 foi realizada administração local de nanoemulsão de própolis verde de baixa viscosidade e nos grupos VEI-PRO2 e ZOL-PRO2, nanoemulsão de própolis verde de alta viscosidade. Foram realizadas 10 sessões de tratamento local, começando imediatamente após a exodontia e a cada 48 horas. No 28° dia pós-operatório, as ratas foram submetidas à eutanásia. As hemimandíbulas esquerdas seguiram para as análises: clínica intra e extrabucal; histopatológica do sítio de extração dental e da mucosa sobrejacente; histométrica de porcentagem de tecido ósseo neoformado (PTONF) e de porcentagem de tecido ósseo não vital (PTONV) no sítio de extração dental e adjacências; e imunoistoquímica para TGF-β1, VEGF, BMP-2/4, OCN, TRAP e NF-κB. Os dados foram submetidos análise estatística com nível de significância de 5%. ZOL apresentou reparo severamente comprometido, reduzida PTONF e alta PTONV. VEI, VEI-PRO1 e VEI-PRO2 apresentaram padrões de reparo, PTONF, PTONV e padrões de imunomarcação semelhantes. ZOL-PRO1 e ZOL-PRO2 tiveram reparo mais favorável, maior PTONF e menor PTONV comparados com ZOL. Os padrões de imunomarcação para ZOL-PRO1 e ZOL-PRO2 foram mais parecidos com VEI que com ZOL. Assim, a nanoemulsão de própolis verde foi capaz de melhorar o curso do reparo alveolar e prevenir o desenvolvimento de lesões osteonecróticas em ratas com os principais fatores de risco para a ONM-M.
Bisphosphonates are anti-resorptive drugs used to treat osteolytic diseases/lesions, whose use has the adverse effect of drug medication-associated osteonecrosis of the jaw (MRONJ). The establishment of effective and safe preventive therapies for MRONJ is important, as its treatment may not be effective. Propolis is a resinous material produced by bees that has antimicrobial, biostimulatory, immunomodulatory, anti-inflammatory and antioxidant actions. Its use in the form of a nanoemulsion, with the objective of improving solubility, absorption and effects, may constitute a promising preventive therapeutic strategy for MRONJ. The aim of the present study was to evaluate the effect of local administration of green propolis nanoemulsion at the dental extraction site of rats with the main risk factors for MRONJ. Sixty female rats were divided into six experimental groups: VEI, VEI-PRO1, VEI- PRO2, ZOL, ZOL-PRO1 and ZOL-PRO2. VEI groups were treated with vehicle (0.9% sodium chloride solution) and ZOL groups with zoledronate (100μg/kg) throughout the experimental period (7 weeks). In all animals, the lower left first molar was subjected to ligature-induced periodontitis and extracted. The VEI and ZOL groups received no local treatment after tooth extraction. In the VEI-PRO1 and ZOL-PRO1 groups, local administration of low-viscosity green propolis nanoemulsion was performed and in the VEI-PRO2 and ZOL-PRO2 groups, high-viscosity green propolis nanoemulsion was administered. Ten local treatment sessions were performed, starting immediately after tooth extraction and every 48 hours. On the 28th postoperative day, the rats were euthanized. The left hemimandibles were processed to allow them to be performed: intra and extraoral clinical analysis; histopathological analysis of the tooth extraction site and overlying mucosa; histometric analysis of the percentage of newly formed bone tissue (PNFBT) and the percentage of non-vital bone tissue (PNVBT) in the tooth extraction site and surrounding areas; and immunohistochemistry for TGF-β1, VEGF, BMP- 2/4, OCN, TRAP e NF-κB. Data were submitted to statistical analysis with a significance level of 5%. ZOL showed severely compromised repair, reduced PNFBT and high PNVBT. VEI, VEI-PRO1 and VEI-PRO2 showed similar repair patterns, PNFBT, PNVBT and immunostaining patterns. ZOL-PRO1 and ZOL-PRO2 had more favorable repair, higher PNFBT and lower PNVBT compared to ZOL. The immunostaining patterns for ZOL-PRO1 and ZOL-PRO2 were more similar to VEI than to ZOL. Thus, the green propolis nanoemulsion was able to improve the course of alveolar repair and prevent the development of osteonecrotic lesions in rats with the main risk factors for MRONJ.
Bisphosphonates are anti-resorptive drugs used to treat osteolytic diseases/lesions, whose use has the adverse effect of drug medication-associated osteonecrosis of the jaw (MRONJ). The establishment of effective and safe preventive therapies for MRONJ is important, as its treatment may not be effective. Propolis is a resinous material produced by bees that has antimicrobial, biostimulatory, immunomodulatory, anti-inflammatory and antioxidant actions. Its use in the form of a nanoemulsion, with the objective of improving solubility, absorption and effects, may constitute a promising preventive therapeutic strategy for MRONJ. The aim of the present study was to evaluate the effect of local administration of green propolis nanoemulsion at the dental extraction site of rats with the main risk factors for MRONJ. Sixty female rats were divided into six experimental groups: VEI, VEI-PRO1, VEI- PRO2, ZOL, ZOL-PRO1 and ZOL-PRO2. VEI groups were treated with vehicle (0.9% sodium chloride solution) and ZOL groups with zoledronate (100μg/kg) throughout the experimental period (7 weeks). In all animals, the lower left first molar was subjected to ligature-induced periodontitis and extracted. The VEI and ZOL groups received no local treatment after tooth extraction. In the VEI-PRO1 and ZOL-PRO1 groups, local administration of low-viscosity green propolis nanoemulsion was performed and in the VEI-PRO2 and ZOL-PRO2 groups, high-viscosity green propolis nanoemulsion was administered. Ten local treatment sessions were performed, starting immediately after tooth extraction and every 48 hours. On the 28th postoperative day, the rats were euthanized. The left hemimandibles were processed to allow them to be performed: intra and extraoral clinical analysis; histopathological analysis of the tooth extraction site and overlying mucosa; histometric analysis of the percentage of newly formed bone tissue (PNFBT) and the percentage of non-vital bone tissue (PNVBT) in the tooth extraction site and surrounding areas; and immunohistochemistry for TGF-β1, VEGF, BMP- 2/4, OCN, TRAP e NF-κB. Data were submitted to statistical analysis with a significance level of 5%. ZOL showed severely compromised repair, reduced PNFBT and high PNVBT. VEI, VEI-PRO1 and VEI-PRO2 showed similar repair patterns, PNFBT, PNVBT and immunostaining patterns. ZOL-PRO1 and ZOL-PRO2 had more favorable repair, higher PNFBT and lower PNVBT compared to ZOL. The immunostaining patterns for ZOL-PRO1 and ZOL-PRO2 were more similar to VEI than to ZOL. Thus, the green propolis nanoemulsion was able to improve the course of alveolar repair and prevent the development of osteonecrotic lesions in rats with the main risk factors for MRONJ.
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Palavras-chave
Osteonecrose, Bisfosfonatos, Exodontia, Propolis, Nanoestruturas, Osteonecrosis, Bisphosphonates, Tooth extrations, Nanostructures