Avaliação do potencial antirreabsortivo de géis de fentolamina e propranolol em reimplantes dentários
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Data
2019-03-20
Autores
Matos, Felipe de Souza [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Este trabalho teve como objetivo avaliar os efeitos da aplicação tópica de fármacos bloqueadores adrenérgicos (AR) sobre o processo de reparo periodontal de dentes reimplantados em ratos. Inicialmente, cultura de fibroblastos do ligamento periodontal humano foi utilizada para avaliar qualitativamente a citotoxicidade de soluções etanólicas de fentolamina (bloqueador α-AR) e propranolol (bloqueador βAR) em diferentes doses (0,75 µg/mL, 2,5 µg/mL, 10 µg/mL e 100 µg/mL), após 24 horas de exposição. Posteriormente, modelo animal de avulsão e reimplante dentário foi utilizado para avaliar o potencial antirreabsortivo do bloqueio adrenérgico local com géis de fentolamina (F) ou propranolol (P), em excipiente de carboximetilcelulose (CMC). Incisivos superiores direitos foram extraídos de 48 ratos Wistar machos, armazenados em guardanapo de papel por 30 minutos, e distribuídos aleatoriamente em oito grupos (n=6) de acordo com a medicação intracanal: F0.75, F10 e F100 receberam gel de fentolamina nas concentrações 0,75 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; P2.5, P10 e P100 receberam gel de propranolol nas concentrações 2,5 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; HC e CMC receberam pasta de hidróxido de cálcio e gel de carboximetilcelulose, respectivamente. Os animais foram eutanasiados 30 dias após o reimplante e as seguintes análises foram realizadas: microtomografia (volume, superfície, proporção e densidade de tecido mineralizado), histomorfometria (áreas de reabsorção radicular inflamatória, reabsorção por substituição, anquilose e reparo periodontal) e histoquímica (atividade osteoclástica). Os dados foram analisados estatisticamente por meio de ANOVA e teste de Tukey ou Kruskal Wallis e teste de Dunn, de acordo com sua normalidade (α=5%). A análise qualitativa da viabilidade celular demonstrou que a dose de 100 µg/mL dos fármacos apresentou alta citotoxicidade, com 100% das células inviáveis, e as demais doses propiciaram viabilidade celular semelhante. As análises microtomográfica e histomorfométrica das amostras in vivo não revelaram qualquer diferença estatística significante entre os fármacos testados e suas diferentes doses (p>0,05). No entanto, P10 e F10 apresentaram qualitativamente um melhor resultado, pois foram os únicos grupos classificados com áreas de intenso reparo periodontal (P10) e de discreta reabsorção radicular inflamatória (F10 e P10). O tratamento com F10 e P10 diminuiu significativamente o número de osteoclastos em comparação com as outras medicações tópicas (p<0,05). Concluiu-se que a aplicação tópica de géis de fentolamina e propranolol na dose de 10 µg/mL diminuiu significativamente a atividade osteoclástica sem causar efeitos citotóxicos.
This study aimed to evaluate the effects of topical application of adrenergic (AR) blocking drugs on the periodontal repair process of replanted teeth in rats. First, culture of human periodontal ligament fibroblasts was used to qualitatively assess the cytotoxicity of ethanolic solutions of phentolamine (α-AR blocker) and propranolol (βAR blocker) at different doses (0.75 μg/mL, 2.5 μg/mL, 10 μg/mL and 100 μg/mL) after 24 hours of exposure. Then, animal model of tooth avulsion and replantation was used to evaluate the anti-resorptive potential of local adrenergic blockade with phentolamine (Ph) or propranolol (Pr) gels, in carboxymethylcellulose excipient (CMC). Maxillary right incisors were extracted from 48 male Wistar rats, stored in paper napkins for 30 minutes, and randomly distributed into eight groups (n = 6) according to intracanal medication: Ph0.75, Ph10 and Ph100 received phentolamine gel at concentrations of 0.75 μg/mL, 10 μg/mL and 100 μg/mL, respectively; Pr2.5, Pr10 and Pr100 received propranolol gel at concentrations of 2.5 μg/mL, 10 μg/mL and 100 μg/mL, respectively; CH and CMC received calcium hydroxide paste and carboxymethylcellulose gel, respectively. The animals were euthanized 30 days after replantation and the following analyzes were performed: microtomography (volume, surface, proportion and density of mineralized tissue), histomorphometry (areas of inflammatory root resorption, replacement root resorption, ankylosis and periodontal repair) and histochemistry (osteoclastic activity). Data were analyzed statistically by means of ANOVA and Tukey's test or Kruskal Wallis and Dunn's test, according to their normality (α = 5%). The qualitative analysis of cell viability demonstrated that the dose of 100 μg/mL of the drugs presented high cytotoxicity, with 100% of the cells non-viable, and the other doses provided similar cell viability. Microtomographic and histomorphometric analyzes of in vivo samples did not reveal any significant statistical difference between the tested drugs and their different doses (p>0.05). However, Pr10 and Ph10 presented qualitatively a better result, as they were the only groups classified with areas of intense periodontal repair (Pr10) and discrete inflammatory root resorption (Ph10 and Pr10). Treatment with Ph10 and Pr10 significantly decreased the number of osteoclasts compared to the other topical medications (p<0.05). It was concluded that topical application of phentolamine and propranolol gels at a dose of 10 μg/mL significantly decreased osteoclastic activity without causing cytotoxic effects.
This study aimed to evaluate the effects of topical application of adrenergic (AR) blocking drugs on the periodontal repair process of replanted teeth in rats. First, culture of human periodontal ligament fibroblasts was used to qualitatively assess the cytotoxicity of ethanolic solutions of phentolamine (α-AR blocker) and propranolol (βAR blocker) at different doses (0.75 μg/mL, 2.5 μg/mL, 10 μg/mL and 100 μg/mL) after 24 hours of exposure. Then, animal model of tooth avulsion and replantation was used to evaluate the anti-resorptive potential of local adrenergic blockade with phentolamine (Ph) or propranolol (Pr) gels, in carboxymethylcellulose excipient (CMC). Maxillary right incisors were extracted from 48 male Wistar rats, stored in paper napkins for 30 minutes, and randomly distributed into eight groups (n = 6) according to intracanal medication: Ph0.75, Ph10 and Ph100 received phentolamine gel at concentrations of 0.75 μg/mL, 10 μg/mL and 100 μg/mL, respectively; Pr2.5, Pr10 and Pr100 received propranolol gel at concentrations of 2.5 μg/mL, 10 μg/mL and 100 μg/mL, respectively; CH and CMC received calcium hydroxide paste and carboxymethylcellulose gel, respectively. The animals were euthanized 30 days after replantation and the following analyzes were performed: microtomography (volume, surface, proportion and density of mineralized tissue), histomorphometry (areas of inflammatory root resorption, replacement root resorption, ankylosis and periodontal repair) and histochemistry (osteoclastic activity). Data were analyzed statistically by means of ANOVA and Tukey's test or Kruskal Wallis and Dunn's test, according to their normality (α = 5%). The qualitative analysis of cell viability demonstrated that the dose of 100 μg/mL of the drugs presented high cytotoxicity, with 100% of the cells non-viable, and the other doses provided similar cell viability. Microtomographic and histomorphometric analyzes of in vivo samples did not reveal any significant statistical difference between the tested drugs and their different doses (p>0.05). However, Pr10 and Ph10 presented qualitatively a better result, as they were the only groups classified with areas of intense periodontal repair (Pr10) and discrete inflammatory root resorption (Ph10 and Pr10). Treatment with Ph10 and Pr10 significantly decreased the number of osteoclasts compared to the other topical medications (p<0.05). It was concluded that topical application of phentolamine and propranolol gels at a dose of 10 μg/mL significantly decreased osteoclastic activity without causing cytotoxic effects.
Descrição
Palavras-chave
Avulsão dentária, Reimplante dentário, Reabsorção radicular, Bloqueadores adrenérgicos, Fentolamina, Propranolol, Tooth avulsion, Tooth replantation, Root resorption, Adrenergic blockers, Phentolamine