The influence of antineoplastic agents on the peri-implant bone around osseointegrated titanium implants: an in vivo histomorphometric and immunohistochemical study.

BACKGROUND AND OBJECTIVE: The interaction between antineoplastic drugs used for treating cancer and non-affected tissues remains poorly assessed and may be critical for maintaining the quality of life for patients during and after treatment. This pre-clinical study evaluated the effects of cisplatin (CIS) and 5-fluorouracil (5-FU) on the peri-implant repair process around osseointegrated titanium implants installed in the tibiae of rats. MATERIAL AND METHODS: Were used 90 male rats, randomly divided into three groups (n = 30): physiological saline solution (PSS), CIS, and 5-FU. Titanium implants (4.0 × 2.2 mm) were inserted in both tibiae of all animals at day 0. The animals received either PSS, CIS, or 5-FU at 35 and 37 days. Euthanasia was performed at 50, 65, and 95 days after surgery. Histometric (bone/implant contact [BIC]) and bone area fraction occupancy (% BAFO), histological, and immunohistochemical (for bone morphogenetic protein 2/4 [BMP2/4], Runt-related transcription factor 2 [RUNX2], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. Data were statistically analyzed. RESULTS: Groups CIS and 5-FU presented lower BIC and lower BAFO as compared with PSS in all time points. The imbalance in bone turnover was observed by the lower number of BMP2/4-, RUNX2-, and OCN-positive cells/mm2 and the higher number of TRAP-positive cells/mm in groups CIS and 5-FU as compared with PSS in all time points. Persistent and exacerbated inflammation was observed in groups CIS and 5-FU. CONCLUSIONS: Both antineoplastic agents interfered negatively in the bone turnover around osseointegrated titanium implants. CLINICAL RELEVANCE: Closer and more careful follow-up of patients with osseointegrated implants that will undergo chemotherapy with either CIS or 5-FU shall be performed.

Antineoplastic agents aggravate the damages caused by nicotine on the peri-implant bone: an in vivo histomorphometric and immunohistochemical study in rats.

OBJECTIVE: To assess the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the treatment of cancer. This study evaluated the influence of cisplatin (CIS) and 5-fluorouracil (5-FU) over the peri-implant tissues around osseointegrated titanium implants in animals previously exposed to nicotine. Materials and methods One hundred twenty male rats were divided into two groups, receiving via subcutaneous injection, either physiological saline solution (PSS) (n = 30) or nicotine hemissulfate (NIC) (n = 90) for 30 days prior to implants' placement. One titanium implant (4.0 × 2.2 mm) was installed in each tibia of all animals. PSS and NIC were continued for 30 days after surgery. Five days after cessation, rats were subdivided into three subgroups in accordance with systemic treatments with either PSS, CIS, or 5-FU. Euthanasia was performed at 50, 65, and 95 days post-surgery. Histometric, histopathological, and immunohistochemical analyses were performed. RESULTS: NIC-CIS and NIC-5FU presented lower BIC (50, 65, and 95 days) and bone area fraction occupancy (BAFO) (65 and 95 days) than group NIC. Intense inflammatory infiltration, severe tissue breakdown, reduced expression of bone formation biomarkers, and upregulation of TRAP were observed in NIC-CIS and NIC-5FU when compared with group NIC. TRAP expression was significantly higher in NIC-5FU as compared with NIC-CIS at 50 and 95 days. Groups NIC, NIC-CIS, and NIC-5FU presented statistically significant negative impact in all outcome parameters than group PSS. CONCLUSION: CIS and 5-FU severely disrupted the peri-implant tissues around osseointegrated implants in animals previously exposed to nicotine. CLINICAL RELEVANCE: Assessing the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the cancer treatment.

Influence of immunosuppression on the progression of experimental periodontitis and on healthy periodontal tissue: A rat in vivo study.

Background. The potent anti-inflammatory and immunosuppressive properties of glucocorticoids (GCs) might influence the progression of some disorders, such as periodontitis. Hence, this study aimed to investigate the influence of dexamethasone (DEX) on the alveolar bone loss (ABL) of healthy and periodontally compromised molars in rats. Methods. Thirty male rats were randomly assigned to two groups: physiological saline solution (PSS) and DEX. The animals received subcutaneous injections of either 0.5 mL of PSS) (group PSS) or 2 mg/kg of DEX (group DEX) from one day before experimental periodontitis (EP) induction until euthanasia. EP was induced through ligature placement around the mandibular lower first molars at day 0. Contralateral molars remained unligated. Ten animals per period were euthanized on days 3, 7, and 14. Morphometric analysis was performed to access the ABL. Data were statistically analyzed with ANOVA followed by post hoc Tukey tests (P ≤ 0.05). Results. Higher ABL was observed in both groups on days 7 and 14 than on day 3 (P ≤ 0.05). Concerning periodontitis, higher ABL was observed in group DEX on days 3, 7, and 14 days than group PSS at the same time intervals (P ≤ 0.05). Also, even in the contralateral unligated molars, group DEX exhibited higher ABL on days 3, 7, and 14 days than group PSS at the same time intervals (P ≤ 0.05). Conclusions. Collectively, it can be concluded that DEX aggravates EP and induces spontaneous ABL in the healthy periodontium.

Platelet-rich fibrin for wound healing of palatal donor sites of free gingival grafts: Systematic review and meta-analysis.

BACKGROUND: Platelet-rich fibrin (PRF) has been referred to as a second-generation platelet concentrate, associated with improvements on the healing of palatal wounds followed by FGG harvesting. The aim of this systematic review and meta-analysis was to assess the complete wound epithelialization and postoperative pain when PRF was used in palatal wounds following free gingival graft (FGG) harvesting. MATERIAL AND METHODS: PubMed (Medline), EMBASE and Scopus were searched by two independent individuals up to and including March 2020 in order to identify controlled and randomized controlled clinical trials on the use of PRF at palatal donor sites of FGG. The outcomes assessed were epithelialization and postoperative pain. The risk of bias of the included studies was evaluated using Cochrane Collaboration's domain-based two-part tool. Random effects meta-analyses were conducted with 95% confidence intervals. RESULTS: The search strategy identified 555 potentially eligible articles, of which 6 randomized controlled clinical trials were included. In the qualitative analysis, most studies (83.3%) reported lower postoperative pain in treatment groups, while all studies accessing epithelialization demonstrated earlier complete wound closure in groups treated with PRF. The discomfort and complete re-epithelialization were more favorable in groups PRF when compared to control groups (P<0.00001). CONCLUSIONS: Within the limits of the present study, it can be concluded that the use of PRF for wound healing of palatal donor sites of FGG may decrease postoperative pain and induce earlier complete wound epithelialization. Key words:Wound healing, oral surgery procedures, pain, postoperative.

Influence of systemic strontium ranelate on the progression and as adjunctive therapy for the nonsurgical treatment of experimental periodontitis.

BACKGROUND: Strontium Ranelate (SR) presents overlapping osteoanabolic and anti-resorptive activity. However, the effects of SR on the progression of periodontitis through the alveolar bone and its potential applicability as adjunctive therapy to scaling and root planning remain poorly accessed. The aim of this study was to evaluate the effects of systemic (SR) both on the progression of experimental periodontitis (EP) and as adjunctive therapy to SRP. MATERIAL AND METHODS: Eighty male rats were divided into four groups (n=20): EP-PSS: EP induction and systemic administration of physiological saline solution (PSS); EP-SR: EP induction and systemic administration of SR; EP-SRP/PSS: EP induction, SRP and systemic administration of PSS; EP-SRP/SR: EP induction, SRP and systemic administration of SR. Seven days after ligature placement, SRP was performed in EP-SRP/PSS and EP-SRP/SR, as well as the systemic administration of either PSS or SR were initiated and continued until euthanasia in all groups. Animals were euthanized at 7 and 30 days after the beginning of the systemic treatments. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (tartrate-resistant acid phosphatase [TRAP], Osteocalcin [OCN] and leukocyte common antigen [CD 45]) analyses were performed. Data were statistically analyzed. RESULTS: EP-SRP/PSS showed a significantly more organized pattern of the connective tissue and alveolar bone structure than EP-SRP/SR. EP-SR showed significantly higher PBF than EP-PSS, however, EP-SRP/PSS showed no difference with EP-SRP/SR at 30 days. CONCLUSIONS: SR reduced the alveolar bone loss in non-treated animals and presented no standout benefits over the conventional forms of treating EP. Key words:Strontium Ranelate, periodontal disease, root planing, alveolar bone loss.

Association of hyaluronic acid with a deproteinized bovine graft improves bone repair and increases bone formation in critical-size bone defects.

BACKGROUND: This study is designed to evaluate the potential of different formulations of hyaluronic acid (HA) to improve new bone formation in critical-size calvaria defect (CSD) when combined with a deproteinized bovine graft (DBG) material. METHODS: Thirty male rats were used. A 5-mm-diameter CSD was created and three experimental groups (n = 10) were randomly assigned based on the treatments performed. Group DBG: CSD filled with a DBG; group DBG/LV: CSD filled by the combination of DBG and HA in a low-viscosity crosslinking agent; group DBG/HV: CSD filled by the combination of DBG and HA in a high-viscosity crosslinking agent. Animals were euthanized 30 days postoperatively. Histological, histometric (percentage of newly formed bone [PNFB], percentage of remaining graft particles, histochemical, and immunohistochemical (bone morphogenetic protein 2/4 [BMP2/4], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. RESULTS: The highest PNFB was observed in DBG/HV when compared with the other groups (P ≤0.05). DBG/LV and DBG/HV presented almost no inflammatory cells. In contrast, inflammation was observed in group DBG. Extensive resorption of graft particles was observed in group DBG, which was not present in DBG/LV and DBG/HV as confirmed by the larger size of the particles (P ≤0.05). BMP2/4 and OCN immunolabeling were higher in DBG/HV when compared with group DBG (P ≤0.05). Increased number of TRAP-positive cells was observed in DBG/LV and DBG/HV (P ≤0.05). Lower percentage of mature collagen fibers was observed in DBG/HV (P ≤0.05). CONCLUSION: The combination of HA in a high-viscosity crosslinking agent with DBG improves the bone repair process and increases the amount of newly formed bone towards CSDs in rat calvaria.

Resposta imunoinflamatória na periodontite experimental induzida em ratos submetidos à quimioterapia e a dose oncológica de zoledronato / Immunoinflammatory response of the experimental periodontitis induced in rats subjected to chemotherapy and anticancer dose of zoledronic acid

O objetivo do presente estudo é avaliar os efeitos da quimioterapia com Cisplatina (CIS) combinado ao uso de Zoledronato (ZOL) sobre os tecidos periodontais saudáveis e na progressão da periodontite experimental induzida em ratos. Foram utilizados 160 ratos machos, distribuídos em dois grupos sem periodontite experimental induzida (SPE) e com periodontite experimental induzida (PE) e subdivididos em quatro subgrupos: SS/SS: receberam duas injeções de 0,5 mL de solução salina a 0.9% (SS) (n= 20); SS/ZOL: receberam uma injeção 0,5 mL de SS e uma injeção de 100 µg/kg de ZOL diluído 0,45 mL em SS (n= 20); CIS/SS: receberam uma injeção de CIS (5mg/kg) e outra injeção de 0,5 mL de SS (n= 20); CIS/ZOL: receberam uma injeção de CIS (5mg/kg) e uma injeção de 100 µg/kg de ZOL diluído 0,45 ml em SS (n= 20). A administação ocorreu por via intraperitoneal em um intervalo de três dias, durante oito semanas. Na quarta semana, foi realizado a indução da PE no primeiro molar inferior esquerdo. Nos períodos de 14 e 28 dias após indução da PE, os animais foram eutanasiados pela administração de dose letal de thiopental (150mg/kg). As mandíbulas obtidas foram fixadas em formaldeído tamponado 4%, descalcificadas em EDTA e incluídas em parafina para confecção de cortes histológicos seriados de 4 µm de espessura para coloração com Hematoxilina e Eosina e realização de reações imunoistoquímicas. Foi realizado análise histológica (escores), histométrica de porcentagem de osso na furca (POF), porcentagem de osso necrosado (PON) e padrões de imunomarcação para TNFα, IL-1ß e TRAP. Os dados obtidos foram submetidos à análise estatística (p<0,05) em programa computacional especializado. Foi observado diminuição do espaço do ligamento periodontal (aos 28 dias) e maior PON (aos 14 e 28 dias) em SPE-SS/ZOL e SPE-CIS/ZOL comparado a SPE-SS/SS e SPE-CIS/SS. Houve menor perda óssea e maior PON em PE-SS/ZOL e PECIS/ZOL comparado a PE-SS/SS e PE-CIS/SS aos 14 e 28 dias. Dentro dos limites do presente estudo, pode-se concluir que o uso combinado de CIS e ZOL é potencial fator de risco para desenvolvimento da osteonecrose dos maxilares, tanto em periodonto saudável quanto em periodonto acometido pela PE(AU)

The objective of the present research was to evaluate the effects of Cisplatin (CIS) chemotherapy combined with zoledronic acid (ZOL) on healthy periodontal tissues and on the progression of experimental periodontitis induced in rats. Were used 160 male rats, divided into two groups, either without induction of experimental periodontitis (NEP) or with induction of experimental periodontitis (EP), and subdivided into 4 subgroups: SS/SS: received two injections of 0.5 mL of saline solution 0.9% (SS) (n=20); SS/ZOL: received one injection of SS and one injection of 100 µg/kg of ZOL solved in 0.45 mL of SS (n=20); CIS/SS: received one injection of CIS (5mg/kg) and one injection of 0.5 mL of SS (n=20); CIS/ZOL: received one injection of CIS (5mg/kg) and one injection of 100 µg/kg of ZOL solved in 0.45 mL of SS (n=20). The drugs/SS were administered via intraperitoneal at 3 days interval, during 8 weeks. On the fouth week, EP was induced in the left mandibular first molar. At 14 and 28 days efter EP induction, the animals were euthanized by lethal dose of sodium thiopental (150mg/kg). The collected mandibles were fixed in buffered 4% formaldehyde solution, demineralized in EDTA and embedded in paraffin for obtention of 4 µm thick semi-serial sections. Then, were submitted to Hematoxylin and Eosin staining and immunohistochemistry. Was performed the following analysis: histologic (scores), histometric of the percentage of bone in the furcation (PBF) and percentage of necrotic bone (PNB), and immunolabelling patter for TNFα, IL-1ß and TRAP. The collected data were submitted to statistical analysis (p<0,05) using an appropriate computer software. Was observed reduction in the periodontal ligament space (at 28 days) and increased PNB (at 14 and 28 days) in NEP-SS/ZOL and NEP-CIS/ZOL when compared with NEP-SS/SS and NEPCIS/SS. Less bone loss and higher PBF was observed in EP-SS/ZOL and EP-CIS/ZOL when compared with EP-SS/SS and EP-CIS/SS at 14 and 28 days. Within the limits of the present research, it can be concluded that combined use of CIS and ZOL is a potential risk factor for the development of medication related osteonecrosis of the jaw both in healthy periodontium and periodontium affected by EP(AU)

Antineoplastic agents exacerbate periodontal inflammation and aggravate experimental periodontitis.

AIM: This study evaluated the effects of 5-fluorouracil (5-FU) and cisplatin (CIS) in healthy periodontal tissues and in the early stages of experimental periodontitis (EP) in rats. METHODS: One hundred and eighty male rats were divided into three groups, which were submitted to the following systemic treatments: physiological saline solution (PSS); CIS and 5FU. Each group was subdivided into two subgroups: without (NEP) and with (EP) induction of EP. Animals were euthanized at 3, 5 and 7 days post-treatment. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tumour necrosis factor-α, interleukin-1ß and receptor activator of nuclear factor-κB ligand) analyses were performed. Data were statistically analysed. RESULTS: CIS-NEP and 5FU-NEP showed more inflammation than PSS-NEP at 3, 5 and 7 days. CIS-EP and 5FU-EP showed more inflammation and lower PBF than PSS-EP at all periods of evaluation. 5FU-EP showed lower PBF than CIS-EP at 5 and 7 days. CONCLUSION: 5-FU and CIS exacerbated periodontal inflammation and aggravated the progression of EP in its early stages.

Dental caries among preschool children: effects of social inequality and the impact of a university extension project / Cárie-dentária em pré-escolares: efeitos das desigualdades sociais e impactos de projeto de extensão universitária

ABSTRACT Objective The aims of this study were to assess the prevalence of dental caries among preschoolers at public and private schools and to evaluate the associations among the prevalence of the disease, socioeconomic factors, and the impact of a university extension project. Methods Five-year-old preschool children were examined and were divided into three groups: children from private schools who were not receiving regular preventive care (group 1), children from public schools who were not receiving regular preventive care (group 2), children from public schools who were receiving preventive care through a university extension project (group 3). The children were examined for decay-missing-filled index, and their caregivers were interviewed to collect data on socioeconomic factors. Fisher's and Chi-squared tests were used to analyze the data. Results Group 1 showed better socioeconomic and oral conditions compared with groups 2 and 3. Parents'/guardians' level of education was associated with the presence of disease in their children; however, income showed no association. Conclusion Dental caries were more prevalent in the group with worse socioeconomic indicators, and although the university extension project had been implemented in one of the groups, it was not able to overcome health inequalities.

RESUMO Objetivo O objetivo deste estudo foi verificar a prevalência da cárie dentária em pré-escolares de escola pública e privada, avaliando sua associação a fatores socioeconômicos e impactos projeto de extensão universitária. Métodos Foram examinados pré-escolares de 5 anos, alocados em 3 grupos: G1 - crianças de colégio privado, sem projeto preventivo em saúde bucal; G2 - crianças de ensino público também sem cuidados preventivos regulares; G3 - pré-escolares de ensino público que recebem cuidados preventivos através de projeto de extensão universitária. As crianças foram examinadas para aferição do índice ceo-d e seus responsáveis foram entrevistados para verificação de fatores socioeconômicos. Para análise dos dados foi utilizado o teste de Fisher e o teste Qui-quadrado Resultados A escola referente ao G1 mostrou melhores condições socioeconômicas e bucais, comparada com os grupos G2 e G3. A escolaridade dos pais esteve associada à presença de doença nos filhos, porém, a renda não demonstrou associação. Conclusão A cárie dentária foi mais prevalente no grupo com piores indicadores socioeconômicos, e apesar do projeto de extensão universitária em saúde bucal estar presente em uma das situações ele não foi capaz de superar as desigualdades em saúde.

pH influences the biocompatibility of methylene blue solutions.

OBJECTIVE: The aim of this study was to investigate the biocompatibility of methylene blue at different pH levels through the method of implantation in subcutaneous tissue. MATERIALS AND METHODS: Eighty-four sterilized polyethylene tubes were allocated in the subcutaneous tissue of 28 rats, each one receiving four tubes, set into four groups: group tube (G-T)-empty tube, fibrin group (G-F)-tube filled with fibrin sponge, group methylene blue pH 7 (G-MB/pH 7)-tube filled with fibrin sponge soaked by methylene blue (100 µg/ml) at pH 7.0, and group methylene blue pH 1 (G-MB/pH 1)-tube filled with fibrin sponge and soaked by methylene blue (100 µg/ml) at pH 1.0. After 7, 15, and 30 days, seven animals from each group were euthanized, and the tubes involved by the surrounding tissue were removed and fixed with 4% buffered formaldehyde solution. The collected pieces were processed and histological sections (4 µm) were stained with hematoxylin and eosin and analyzed by light microscopy. Scores were assigned to analysis of histopathologic parameters. The results were statistically analyzed by the Kruskal-Wallis test (p ≤ 0.05). RESULTS: At 7 and 30 days, the G-MB/pH 1 group showed no significant difference in the G-T control group, while G-MB/pH 7 had a significant increase on tissue reaction, also when compared to G-T. At 15 days, there was no statistical difference between the groups. CONCLUSION: Within the limits of this study, it is concluded that methylene blue at pH 1.0 provides better biocompatibility than at pH 7.0.

Influence of low-level laser therapy on the healing process of autogenous bone block grafts in the jaws of systemically nicotine-modified rats: A histomorphometric study.

OBJECTIVE: To analyze the influence of low-level laser therapy (LLLT) on the bone healing process of autogenous bone block grafts installed in nicotine systemically modified rats. METHODS: Seventy-two rats (Wistar) were randomly assigned into 4 groups (n=18). SS-BG: saline application+bone graft. SS-BG/LLLT: saline application+bone graft+LLLT. NIC-BG: nicotine application+bone graft. NIC-BG/LLLT: nicotine application+bone graft+LLLT. After 30days of application of solutions, all animals received autogenous bone block graft in the jaw, with the donation from the parietal bone's calvarial area. Treatment with LLLT was in bed-graft interface, after accommodation of the graft. The animals in each group were sacrificed at 7, 14, and 28days after graft surgery. RESULTS: The histologic analyses of NIC-BG group depicted a delay of osteogenic activity in the recipient bed-graft interface and the irradiation of tissue with LLLT provided better bone healing. The histometric analysis revealed that SS-BG/LLLT and NIC-BG/LLLT groups showed increased bone formation compared to BG-SS and NIC-BG groups, after 14days (SS-BG 24.94%±13.06% versus SS-BG/LLLT 27.53%±19.07% and NIC-BG 14.27%±2.22% versus NIC-BG/LLLT 24.37%±11.93%) and 28days (SS-BG 50.31%±2.69% versus SS-BG/LLLT 58 19%±12.32% and NIC-BG 36.89%±8.40% versus NIC-BG/LLLT 45.81%±6.03%). CONCLUSION: Nicotine harms bone formation in the bed-graft interface and LLLT action can mitigate this.

Resposta imunoinflamatória na periodontite experimental induzida em ratos submetidos à quimioterapia: estudo histomorfométrico e imunoistoquímico / Immunoinflammatory response in induced experimental periodontitis in rats submitted to chemotherapy: histomorphometric and immunohistochemical study

O presente estudo tem por objetivo avaliar o efeito dos quimioterápicos 5-Fluorouracil (5-FU) e da Cisplatina (CIS) sob os tecidos periodontais saudáveis e durante os estágios inicias da periodontite experimental (PE) induzida em ratos. No presente estudo, foram utilizados 156 ratos machos, distribuídos aleatoriamente em 6 grupos: SPE-SS (n= 26): sem indução da PE e que receberam administração de solução salina (grupo Sham); SPE-CIS (n= 21) ­ sem indução da PE e que receberam administração de CIS; SPE5FU (n= 27) ­ sem indução da PE e que receberam administração de 5-FU; PE-SS (n= 27): indução da PE e que receberam administração de solução salina; PE-CIS (n= 28) - indução da PE e que receberam administração de CIS; PE-5FU (n= 27) - indução da PE e que receberam administração de 5-FU. Os animais receberam 2 injeções para administração dos quimioterápicos com intervalo de 48 horas entre elas (períodos: baseline e 02 dias), aplicando-se as doses de 5 mg/kg e 2,5mg/kg (CIS) e 60 mg/kg e 40 mg/kg (5-FU). Logo após a primeira injeção, foi realizado a indução da PE adaptado-se um fio de algodão número 24 ao redor do primeiro molar inferior esquerdo. Nos períodos de 03, 05 e 07 dias após indução da PE, os animais foram eutanasiados pela administração de dose letal de thiopental (150mg/kg). Para análise hematológica de leucócitos totais (LT), foram obtidas amostras sanguíneas no baseline e no último período de eutanásia e para fosfatase alcalina (FA) no baseline e em todos os períodos experimentais. As mandíbulas obtidas foram fixadas em formaldeído tamponado 4%, descalcificadas em EDTA e incluídas em parafina para confecção de cortes histológicos seriados de 4 µm de espessura no sentido mésio-distal para coloração com Hematoxilina e Eosina e realização de reações imunoistoquímicas. Foi realizado análise histológica (escores), histométrica de porcentagem de osso na furca (POF) e padrões de imunomarcação para TNFα, IL-1ß e RANKL (escores). Os dados obtidos foram submetidos à análise estatística (p<0,05) em programa computacional especializado. Observou-se uma diminuição nos níveis de LT nos grupos SPE-5FU e PE-5FU aos 7 dias. A FA sérica diminuiu aos 3, 5 e 7 dias nos grupos SPE-CIS, SPE-5FU, PE-SS, PECIS e PE-5FU. Histologicamente, SPE-CIS e SPE-5FU obtiveram uma exacerbação do processo inflamatório comparado ao SPE-SS, isso foi condizente com os resultados imunoistoquímicos, com maior padrão de imunomarcação para TNFα e IL-1ß. Para PECIS e PE-5FU houve maior exacerbação do processo inflamatório comparados com os demais grupos, isso foi condizente com os resultados imunoistoquímicos, com maior padrão de imunomarcação para TNFα e IL-1ß aos 3 e 7 dias e RANKL aos 7 dias. Deste modo, houve menor POF nos grupos PE-CIS e PE-5FU comparado ao PE-SS em todos períodos experimentais, além disso, PE-5FU apresentou menor POF até mesmo comparado ao PE-CIS aos 5 e 7 dias. Diante dos limites do presente estudo, pode-se concluir que os quimioterápicos promoveram uma exacerbação do processo inflamatório nos tecidos periodontais saudáveis e agravaram a progressão da PE em seu estágio inicial(AU)

The aim of the present study was to evaluate the effect of the chemotherapics 5- Fluorouracil (5-FU) and Cisplatin (CIS) on healthy periodontal tissues and during the early stages of induced experimental periodontitis (EP) in rats. 156 male rats were randomly set in 6 groups: NP-SS (n = 26): without EP induction and received saline solution (Sham group); NP-CIS (n = 21) - without EP induction and received CIS; NP5FU (n = 27) - without EP induction and received 5-FU; EP-SS (n = 27): induction of EP and received saline solution; EP-CIS (n = 28) - induction of EP and received CIS; EP-5FU (n = 27) - induction of PE and received 5-FU. The animals received 2 injections of chemotherapics with 48-hour interval between them, with doses of 5 mg/kg and 2.5 mg/kg (CIS) and 60 mg/kg and 40 mg/kg (5-FU). After the first injection, the induction of EP was performed by the placement of a number 24 cotton thread around the lower left first molar. At 03, 05 and 07 days after EP induction the animals were euthanized by administration of thiopental (150mg/kg). For hematological analysis of total leukocytes (TL), blood samples were obtained at baseline and in the last euthanasia period, and for Alkaline Phosphatase (AP), at baseline and in all experimental periods. The collected mandibles were fixed in buffered 4% formaldehyde, demineralized in EDTA and embedded in paraffin for preparation of serial histological sections of 4 µm thickness in mesiodistal direction for Hematoxylin and Eosin staining and immunohistochemical reactions. Histotologic (scores), histometry of the percentage of bone in the furcation (PBF) and immunolabelling standards for TNFα, IL-1ß and RANKL (scores) analyzes were performed. The data were submitted to statistical analysis (p <0.05) in a specialized computer program. A decrease of the TL levels in NP-5FU and EP-5FU groups was observed at 7 days. Serum AP decreased at 3, 5 and 7 days in NP-CIS, NP-5FU, EP-SS, EP-CIS and EP5FU. Histologically, NP-CIS and NP-5FU presented an exacerbation of the inflammatory process compared to the NP-SS, this was consistent with the immunohistochemical results, with higher immunolabelling pattern of TNFα and IL-1ß. In EP-CIS and EP-5FU was observed an increased exacerbation of the inflammatory process compared to the other groups, this was consistent with the immunohistochemical results, with a higher immunolabelling pattern for TNFα and IL1ß at 3 and 7 days, and RANKL at 7 days. Thus, there was a smaller POF in EP-CIS and EP-5FU compared to the EP-SS in all experimental periods, moreover, EP-5FU presented smaller POF even compared to EP-CIS at 5 and 7 days. Given the limitations of the present study, it can be concluded that chemotherapy exacerbated the inflammatory process in healthy periodontal tissues and aggravated the progression of EP in its initial stage(AU)