Avaliação do reparo ósseo peri-implantar em ratos tratados com quimioterapia e dose oncológica de zoledronato.
Carregando...
Data
2021-05-04
Autores
Araujo, Nathália Januario de [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O objetivo do presente estudo foi avaliar a influencia da terapia sistêmica com zoledronato, cisplatina, ou a associação das drogas, sobre o processo de reparo ósseo peri-implantar ao redor de implantes instalados em tíbias de ratos. Foram utilizados 80 ratos machos, com 6 meses de idade, pesando aproximadamente 450g. Os animais foram separados em 2 grandes grupos experimentais, grupo Tardio (TAR) e grupo Imediato (IME) e divididos nos seguintes subgrupos onde receberam os seguintes tratamentos: Grupo SAL-IME (n=10), Grupo SAL-TAR (n=10): duas injeções de 0,5 ml de solução salina a 0.9%; Grupo CIS-IME (n=10), Grupo CIS-TAR (n=10): uma injeção de Cisplatina (5mg/kg) e outra injeção de 0,5 ml de solução salina a 0.9%; Grupo ZOL-IME (n=10), Grupo ZOL-TAR (n=10): uma injeção 0,5 ml de solução salina a 0.9% e uma injeção de 100 μg/kg de zoledronato diluído 0,45 ml em solução de cloreto de sódio 0,9%; Grupo ZOL/CIS-IME (n=10), Grupo ZOL/CIS-TAR (n=10): uma injeção de Cisplatina (5mg/kg) e uma injeção de 100 μg/Kg de zoledronato diluído 0,45 ml em solução de cloreto de sódio 0,9%. A administação ocorreu por via intraperitoneal em um intervalo de três dias, durante oito semanas. Após 16 semanas do início do tratamento medicamentoso, os animais foram submetidos a instalação dos implantes nas tíbias direitas e esquerdas sob anestesia geral. Decorridos 16 semanas (grupo IME) e 24 semanas (grupo TAR) do início do tratamento medicamentoso, os animais foram submetidos à eutanásia pela administração de dose letal de thiopental (150mg/kg). As tíbias direitas e esquerdas foram coletadas e fixadas em formaldeído 4% e processadas de acordo com as análises propostas. A condição geral de saúde foi verificada durante todo o período experimental através do monitoramento do peso corporal e um minucioso exame clínico da região peri-implantar nas tíbias direita e esquerda foi realizado no momento das eutanásias. As tíbias selecionadas para análise histométrica do contato direto entre osso e implante foram processadas sem desmineralização. Os espécimes restantes foram submetidos ao processamento histológico convencional, constituído por desmineralização e inclusão em parafina. Foram realizadas secções semi seriadas de 4 µm de espessura em direção longitudinal à loja do implante, e os corteshistológicos foram selecionados e corados pelo método da Hematoxilina Eosina para as análises histopatológica dos tecidos peri-implantares e histométrica do tecido ósseo. Os dados obtidos foram submetidos à análise estatística (p≤0,05) em programa computacional especializado (Bioestat 5.0). Os animais pertencentes aos grupos CIS IME e CIS-TAR, apresentram menor peso quando comparados aos demais grupos. O grupo ZOL-IME, ZOL-TAR, apresentaram maior porcentagem de tecido ósseo total (PTO-T) em comparação a CIS-IME e CIS-TAR, ZOL/CIS-IME e ZOL/CIS TAR apresentaram maior porcentagem de tecido ósseo não vital (PTO-NV) quando comparados aos demais grupos. Os grupos CIS-IME e CIS-TAR apresentarm menor contato osso/implante (COI) quando comparados aos demais grupos. Deste modo conclui se que, a associação desses medicamentos é um potencial fator de risco para desenvolvimento da osteonecrose dos maxilares e de acordo com as análises histopatológicas e de COI apresenta comprometimento mais severo aos tecidos peri implantares.
The aim of the present study was to evaluate the influence of systemic therapy with zoledronate, cisplatin, or the combination of drugs, on the peri-implant bone repair process around implants installed in rat tibiae. Eighty male rats, 6 months old, weighing approximately 450g, were used. The animals were separated into 2 large experimental groups, Late group (TAR) and Immediate group (IME) and divided into the following subgroups where they received the following treatments: SAL-IME Group (n = 10), SAL-TAR Group (n = 10 ): two injections of 0.5 ml of 0.9% saline; : CIS-IME Group (n = 10), CIS-TAR Group (n = 10): an injection of Cisplatin (5mg / kg) and another injection of 0.5 ml of 0.9% saline; ZOL-IME Group (n = 10), ZOL-TAR Group (n = 10): an injection of 0.5 ml of 0.9% saline and an injection of 100 μg / kg of zoledronate diluted 0.45 ml in solution of 0.9% sodium chloride; : ZOL / CIS-IME Group (n = 10), ZOL / CIS TAR Group (n = 10): an injection of Cisplatin (5mg / kg) and an injection of 100 μg / kg of diluted zoledronate 0.45 ml in 0.9% sodium chloride solution. The administration took place intraperitoneally over an interval of three days, for eight weeks. After 16 weeks from the beginning of drug treatment, the animals were submitted to the implantation of implants in right and left tibiae under general anesthesia. After 16 weeks (IME group) and 24 weeks (TAR group) after the beginning of drug treatment, the animals were euthanized by the administration of a lethal dose of thiopental (150mg / kg). The right and left tibiae were collected and fixed in 4% formaldehyde and processed according to the proposed analyzes. The general health condition was verified throughout the experimental period by monitoring body weight and a thorough clinical examination of the peri-implant region in the right and left tibia was performed at the time of euthanasia. The tibiae selected for histometric analysis of the direct contact between bone and implant were processed without demineralization. The remaining specimens were submitted to conventional histological processing, consisting of demineralization and inclusion in paraffin. Semi-serial sections of 4 µm thick were made in the longitudinal direction to theimplant store, and the histological sections were selected and stained by the Hematoxylin Eosin method for the histopathological analysis of the peri-implant tissues and histometric of the newly formed bone tissue. The data obtained were submitted to statistical analysis (p≤0.05) in a specialized computer program (Bioestat 5.0). The CIS-IME and CIS-TAR groups had less weight when compared to the other groups. The ZOL-IME group, ZOL-TAR, had higher PTO-T compared to CIS-IME and CIS-TAR, ZOL / CIS-IME and ZOL / CIS TAR had higher PTO-NV when compared to the other groups. The CIS-IME and CIS TAR groups had lower bone implant contact (COI) when compared to the other groups. Thus, it is concluded that the combination of these drugs is a potential risk factor for the development of osteonecrosis of the jaws and, according to the histopathological and COI analyzes, it presents more severe impairment to the peri-implant tissues.
The aim of the present study was to evaluate the influence of systemic therapy with zoledronate, cisplatin, or the combination of drugs, on the peri-implant bone repair process around implants installed in rat tibiae. Eighty male rats, 6 months old, weighing approximately 450g, were used. The animals were separated into 2 large experimental groups, Late group (TAR) and Immediate group (IME) and divided into the following subgroups where they received the following treatments: SAL-IME Group (n = 10), SAL-TAR Group (n = 10 ): two injections of 0.5 ml of 0.9% saline; : CIS-IME Group (n = 10), CIS-TAR Group (n = 10): an injection of Cisplatin (5mg / kg) and another injection of 0.5 ml of 0.9% saline; ZOL-IME Group (n = 10), ZOL-TAR Group (n = 10): an injection of 0.5 ml of 0.9% saline and an injection of 100 μg / kg of zoledronate diluted 0.45 ml in solution of 0.9% sodium chloride; : ZOL / CIS-IME Group (n = 10), ZOL / CIS TAR Group (n = 10): an injection of Cisplatin (5mg / kg) and an injection of 100 μg / kg of diluted zoledronate 0.45 ml in 0.9% sodium chloride solution. The administration took place intraperitoneally over an interval of three days, for eight weeks. After 16 weeks from the beginning of drug treatment, the animals were submitted to the implantation of implants in right and left tibiae under general anesthesia. After 16 weeks (IME group) and 24 weeks (TAR group) after the beginning of drug treatment, the animals were euthanized by the administration of a lethal dose of thiopental (150mg / kg). The right and left tibiae were collected and fixed in 4% formaldehyde and processed according to the proposed analyzes. The general health condition was verified throughout the experimental period by monitoring body weight and a thorough clinical examination of the peri-implant region in the right and left tibia was performed at the time of euthanasia. The tibiae selected for histometric analysis of the direct contact between bone and implant were processed without demineralization. The remaining specimens were submitted to conventional histological processing, consisting of demineralization and inclusion in paraffin. Semi-serial sections of 4 µm thick were made in the longitudinal direction to theimplant store, and the histological sections were selected and stained by the Hematoxylin Eosin method for the histopathological analysis of the peri-implant tissues and histometric of the newly formed bone tissue. The data obtained were submitted to statistical analysis (p≤0.05) in a specialized computer program (Bioestat 5.0). The CIS-IME and CIS-TAR groups had less weight when compared to the other groups. The ZOL-IME group, ZOL-TAR, had higher PTO-T compared to CIS-IME and CIS-TAR, ZOL / CIS-IME and ZOL / CIS TAR had higher PTO-NV when compared to the other groups. The CIS-IME and CIS TAR groups had lower bone implant contact (COI) when compared to the other groups. Thus, it is concluded that the combination of these drugs is a potential risk factor for the development of osteonecrosis of the jaws and, according to the histopathological and COI analyzes, it presents more severe impairment to the peri-implant tissues.
Descrição
Palavras-chave
Implantes dentários, Quimioterapia, Difosfonatos, Dental implants