Influência de drogas quimioterápicas na evolução da periodontite experimental em ratos
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Data
2017-09-01
Autores
Novaes, Vivian Cristina Noronha [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Objetivo: Este estudo avaliou comparativamente a influência dos quimioterápicos 5-fluotouracil (5-FU) e Cisplanina (CIS) para tratamento de câncer no periodonto saudável, sobre a evolução da periodontite experimental (PE) e as funções hepáticas e renais de ratos portadores de PE submetidos ao tratamento com os quimioterápicos 5-FU ou CIS. Materiais e Métodos: foram utilizado 90 ratos machos distribuídos em 6 grupos. Grupo SPE-SS (n = 15): animais que receberam injeções de 0,5 ml de solução salina 0.9% (SS) sem indução da PE (grupo Sham). Grupo PE-SS (n = 15): animais que receberam injeções s de 0,5 ml de SS e indução da PE após a primeira injeção. Grupo SPE-5FU (n=15): animais que receberam injeções de 5-Fluorouracil (5- FU) sem indução da PE. Grupo PE-5FU (n = 15): animais que receberam injeções de 5- FU e indução da PE após a primeira injeção. Grupo SPE-CIS (n = 15): animais que receberam injeções Cisplatinas (CIS) sem indução da PE. Grupo PE-CIS (n = 15): animais que receberam injeções de CIS e indução da PE após a primeira injeção. Para indução da PE foi adaptado um fio de algodão número 24 ao redor dos primeiros molares inferiores direito e esquerdo. Decorridos 07, 15 e 30 dias após a primeira injeção intraperitoneal (SS ou quimioterápicos) os animais foram eutanaziados. Foi realizada coleta sanguínea para análises hematológia e bioquímicas de aspartato aminotransferase (AST), alamina aminotransferase (ALT), creatinina e uréia previamente as injeções e aos 07 e 30 dias, totalizando 60 dos 90 ratos. Foram coletadas as mandíbulas contendo os primeiros molares inferiores e processadas de acordo com as análises propostas. Para a análise fotométrica avaliou-se a perda óssea alveolar ao redor do primeiro molar inferior. Para a análise de microtomografia computadorizada (µCT) avaliou-se a porcentagem de volume de tecido ósseo (PVTO) na região de furca. As hemimandíbulas contralaterais foram utilizadas para análises histomorfométrica e imunoistoquímicas na região de furca e avaliou-se a porcentagem de área sem osso (PASO), características histológicas e análises dos biomarcadores (TRAP, RANKL, OPG, TNF-α, IL-1β, PCNA, BAX e HIF-1α,). Os dados obtidos foram submetidos à análise estatística (p<0,05). Resultado: ambos os quimioterápicos 5-FU e CIS contribuíram para o agravamento da evolução da PE por duas vias: aumentando a intensidade e duração do processo inflamatório; e diminuindo a capacidade de reparo tecidual por redução do “turnover” celular e vascular, resultando de forma significativa na maior perda óssea, que comparativamente foi maior nos animais que receberam aplicação sistêmica de 5-FU do que de CIS. Adicionalmente a PE associada ao 5-FU apresentou de maneira significante maiores níveis de ALT e AST aos 30 dias e associada a CIS apresentou de maneira significante maiores níveis de Uréia e não apresentou diferença significativa nos níveis de Creatinina. Conclusão: ambos os quimioterápicos, 5-FU ou CIS, exacerbaram a severidade da periodontite, sendo que os danos periodontais causadas pelo 5-FU foram comparativamente maiores e mais intensos do que os causados pela CIS. Adicionalmente, podemos concluir que a PE agravou de forma sinérgica as condições debilitantes hepáticas e renais ocasionadas pelos quimioterápicos.
Objective: This study evaluated the influence of chemotherapy with 5-fluorotouracil (5- FU) and Cisplanin (CIS) for the treatment of cancer in healthy periodontium, on the evolution of experimental periodontitis (EP), and liver and kidney function of rats with EP treated with chemotherapeutic agents. Materials and Methods: 90 male rats were distributed in 6 groups. Group SPE-SS (n = 15): animals that received injections of 0.5 ml of 0.9% saline solution (SS) without PE induction (Sham group). Group PE-SS (n = 15): animals that received injections s of 0.5 ml of SS and induction of PE after the first injection. Group SPE-5FU (n = 15): animals receiving injections of 5-Fluorouracil (5- FU) without induction of PE. Group PE-5FU (n = 15): animals receiving injections of 5- FU and induction of PE after the first injection. SPE-CIS group (n = 15): animals that received Cisplatin injections (CIS) without PE induction. PE-CIS group (n = 15): animals that received CIS injections and PE induction after the first injection. For EP induction a cotton thread number 24 was fitted around the first right and left lower first molars. After 07, 15 and 30 days after the first intraperitoneal injection (SS or chemotherapeutic) the animals were euthanized. Blood samples were collected for hematological and biochemical analyzes of AST, ALT, creatinine and urea before injections and at 07 and 30 days. The mandibles containing the mandibular first molars were collected and processed according to the proposed analyzes. For the photometric analysis, alveolar bone loss (ABL) around the lower first molar was evaluated. For the analysis of computerized microtomography (µCT) the percentage of bone tissue volume (PBTV) in the furcation region was evaluated. The contralateral hemimandibula were used for histomorphometric and immunohistochemical analyzes in the furcation region and the percentage of bone-free area (PBFA), histological characteristics and biomarkers analysis (TRAP, RANKL, OPG, TNF-α, IL-1β, PCNA, BAX and HIF-1α). Data were submitted to statistical analysis (p <0.05). Results: Both chemotherapy 5-FU and CIS contributed to the worsening of the evolution of EP by two routes: increasing the intensity and duration the inflammatory process; and decreased tissue repair ability by reducing cell and vascular turnover, resulting in significantly greater bone loss, which was comparatively higher in animals treated with 5-FU than in CIS. Additionally, 5-FU associated PE significantly increased ALT and AST levels at 30 days and associated CIS significantly increased Urea levels and showed no significant difference in Creatinine levels. Conclusion: both chemotherapy, 5-FU or CIS, exacerbated the severity of periodontitis, and periodontal damage caused by 5-FU was comparatively bigger and faster than those caused by CIS. In addition, we can conclude that PE has synergistically aggravated the liver and kidney debilitating conditions caused by chemotherapy.
Objective: This study evaluated the influence of chemotherapy with 5-fluorotouracil (5- FU) and Cisplanin (CIS) for the treatment of cancer in healthy periodontium, on the evolution of experimental periodontitis (EP), and liver and kidney function of rats with EP treated with chemotherapeutic agents. Materials and Methods: 90 male rats were distributed in 6 groups. Group SPE-SS (n = 15): animals that received injections of 0.5 ml of 0.9% saline solution (SS) without PE induction (Sham group). Group PE-SS (n = 15): animals that received injections s of 0.5 ml of SS and induction of PE after the first injection. Group SPE-5FU (n = 15): animals receiving injections of 5-Fluorouracil (5- FU) without induction of PE. Group PE-5FU (n = 15): animals receiving injections of 5- FU and induction of PE after the first injection. SPE-CIS group (n = 15): animals that received Cisplatin injections (CIS) without PE induction. PE-CIS group (n = 15): animals that received CIS injections and PE induction after the first injection. For EP induction a cotton thread number 24 was fitted around the first right and left lower first molars. After 07, 15 and 30 days after the first intraperitoneal injection (SS or chemotherapeutic) the animals were euthanized. Blood samples were collected for hematological and biochemical analyzes of AST, ALT, creatinine and urea before injections and at 07 and 30 days. The mandibles containing the mandibular first molars were collected and processed according to the proposed analyzes. For the photometric analysis, alveolar bone loss (ABL) around the lower first molar was evaluated. For the analysis of computerized microtomography (µCT) the percentage of bone tissue volume (PBTV) in the furcation region was evaluated. The contralateral hemimandibula were used for histomorphometric and immunohistochemical analyzes in the furcation region and the percentage of bone-free area (PBFA), histological characteristics and biomarkers analysis (TRAP, RANKL, OPG, TNF-α, IL-1β, PCNA, BAX and HIF-1α). Data were submitted to statistical analysis (p <0.05). Results: Both chemotherapy 5-FU and CIS contributed to the worsening of the evolution of EP by two routes: increasing the intensity and duration the inflammatory process; and decreased tissue repair ability by reducing cell and vascular turnover, resulting in significantly greater bone loss, which was comparatively higher in animals treated with 5-FU than in CIS. Additionally, 5-FU associated PE significantly increased ALT and AST levels at 30 days and associated CIS significantly increased Urea levels and showed no significant difference in Creatinine levels. Conclusion: both chemotherapy, 5-FU or CIS, exacerbated the severity of periodontitis, and periodontal damage caused by 5-FU was comparatively bigger and faster than those caused by CIS. In addition, we can conclude that PE has synergistically aggravated the liver and kidney debilitating conditions caused by chemotherapy.
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Palavras-chave
Perda óssea alveolar, Doenças periodontais, Defeito de furca, Quimioterapia, Modelo animal, Alveolar bone loss, Periodontal disease, Chemotherapy, Furcation defect, Animal models