Side effects of different head and neck radiotherapy doses on wistar rat's behavior.

Radiotherapy (RT) is a common treatment for head and neck tumors. However, it causes several physical and behavioral side effects, and no study has assessed the emotional effects in rats. Therefore, the present study evaluated the influence of head and neck RT on the behavior and body weight gain in Wistar rats. Fifty-four male Wistar rats were allocated into six groups (n = 9) according to the irradiation dose, which was applied at the first day of the experiment: RT-7.5 (single dose of 7.5 Gy); RT-10 (single dose of 10 Gy); RT-15 (single dose of 15 Gy); RT-30 (single dose of 30 Gy); Control (without RT). The animals were irradiated in the region of the right face, and behavioral tests and weighing were performed on days one, seven, and 28. The open field and Y-maze tests were undertaken to analyze the animal's behavior. The dose of 30 Gy was lethal when applied to the head and neck region. The irradiated animals had less weight gain when compared to the control ones, but there was no statistical difference. In the open field and Y-maze tests, lower mobility of animals in the RT groups was observed both on day seven and at the end of the experiment (day 28) when compared to the control rats (p < 0.05). It was possible to conclude that the different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups, however, without statistical difference.

Effect of radiotherapy on the differentiation and osteogenic activity of mesenchymal stem cells on dental implants / Efeito da radioterapia na diferenciação e atividade osteogênica de células-tronco mesenquimais em implantes dentários

Objective: to evaluate the differentiation and gene expression of transcripts related to osteogenesis in a primary culture of Mesenchymal Stem Cells (MSCs) derived from rat femurs submitted to radiotherapy and the installation of pure titanium implants. Material and Methods: fifty-four rats received titanium implants in both femurs and were divided into three groups: Control: implant surgery (C); Implant + immediate irradiation (IrI), and Implant + late irradiation (IrL). Euthanasia occurred 3, 14, and 49 days after surgery. The bone marrow MSCs from the femurs were isolated and cultivated. The cell viability, total protein content, alkaline phosphatase (ALP) activity, and the formation of mineralization nodules and cellular genotoxicity were analyzed. The gene expression of Alkaline Phosphatase (phoA), Collagen 1 (COL1), Runt-related transcription factor 2 (RUNX2), Osterix (OSX), Osteopontin (OPN), Integrin ß1(ITGB1), Bone Sialoprotein (BSP), Osteonectin (SPARC), Osteocalcin (Bglap), Transforming Growth Factor ß-type (TGF-ß), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), Interleukin-6 (IL-6), Apolipoprotein E (APOE) and Prostaglandin E2 synthase (PGE2) were evaluated by qRT- PCR. Results: ionizing radiation suppresses the gene expression of essential transcripts for bone regeneration, as well as cellular viability, as observed in the IrI and IrL groups. Conclusion: although this can lead to the loss of osseointegration and failure of the implant, the MSCs showed more activity at 49 days than at 3 and 14 days. (AU)

Objetivo: avaliar a diferenciação e expressão gênica de transcritos relacionados à osteogênese em cultura primária de MSCs derivadas de fêmures de ratos submetidos à radioterapia e instalação de implantes de titânio puro. Material e Métodos: cinquenta e quatro ratos receberam implantes de titânio em ambos os fêmures e foram divididos em três grupos: Controle: cirurgia de implante (C); Implante + irradiação imediata (IrI) e Implante + irradiação tardia (IrL). A eutanásia ocorreu 3, 14 e 49 dias após a cirurgia. As MSCs de medula óssea dos fêmures foram isoladas e cultivadas. Foram analisadas a viabilidade celular, teor de proteína total, atividade da fosfatase alcalina (ALP), formação de nódulos de mineralização e genotoxicidade celular. A expressão gênica de Fosfatase Alcalina (phoA), Colágeno 1 (COL1), fator de transcrição relacionado a Runt 2 (RUNX2), Osterix (OSX), Osteopontina (OPN), Integrina ß1 (ITGB1), Sialoproteína Óssea (BSP), Osteonectina (SPARC), Osteocalcina (Bglap), Fator de Crescimento Transformador tipo ß (TGF-ß), Fator Estimulante de Colônia de Granulócitos-Macrófagos (GM-CSF), Interleucina-6 (IL-6), Apolipoproteína E (APOE) e Prostaglandina E2 sintase (PGE2) foram avaliados por qRT-PCR. Resultados: a radiação ionizante suprime a expressão gênica de transcritos essenciais para a regeneração óssea, bem como a viabilidade celular, como observado nos grupos IrI e IrL. Conclusão:embora isso possa levar à perda da osseointegração e falha do implante, as MSCs apresentaram maior atividade aos 49 dias do que aos 3 e 14 dias (AU)

Systemic and local effects of radiotherapy: an experimental study on implants placed in rats.

OBJECTIVES: Evaluate the modulating effect of ionizing radiation, blood cytokine levels, and bone remodeling of the interface around the implant to understand the radiation mechanisms which can impair the implants receptor site. MATERIAL AND METHODS: Sixty rats were submitted to grade V titanium implants in the femurs and were divided into the following groups: no-irradiation (N-Ir): control group with implant only; early-irradiation (E-Ir): implant + irradiation after 24 h; late-irradiation (L-Ir): implant + irradiation after 4 weeks; and previous-irradiation (P-Ir): irradiation + implant after 4 weeks. The animals in the E-Ir, L-Ir, and P-Ir groups were irradiated in two fractional stages of 15 Gy. At 3 days, 2 weeks, and 7 weeks after the final procedure, five animals were randomly euthanized per group. Serum levels of TNF-ɑ, IL-1ß, TGF-ß, IL-6, M-CSF, and IL-10 were measured from blood collected prior to euthanasia using the ELISA test. The pieces containing the implants were subjected to immunohistochemical labeling using the tartrate acid resistant to phosphatase, osteocalcin, and caspase-3 markers and mCT. The ANOVA test was used for statistical analysis, and the Tukey multiple comparison test (p < 0.05) was applied. RESULTS: The results indicated that ionizing radiation modifies the production of pro- and anti-inflammatory serum cytokines, the expression of proteins involved in bone remodeling and cellular apoptosis, as well as changes in bone formation. CONCLUSIONS: The results suggests that a longer period between radiotherapy and implant placement surgery when irradiation occurs prior to implant installation would allow the recovery and renewal of bone cells and avoid future failures in osseointegration. CLINICAL RELEVANCE: The search for modifications caused by ionizing irradiation in bone tissue can indicate the ideal period for implant placement without affecting the osseointegration process.