RESUMO
PURPOSE: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. METHODS: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. RESULTS: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1ß and TNF-ß levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. CONCLUSIONS: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.
Assuntos
Analgésicos , Anti-Inflamatórios , Antineoplásicos , Apoptose , Sobrevivência Celular , Quinoxalinas , Animais , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/farmacologia , Camundongos , Apoptose/efeitos dos fármacos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/análise , Masculino , Células HT29 , Ensaio de Imunoadsorção Enzimática , Peritonite/tratamento farmacológicoRESUMO
ABSTRACT Purpose: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. Methods: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. Results: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1β and TNF-β levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. Conclusions: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.
RESUMO
Este trabalho objetivou desenvolver, caracterizar e avaliar a atividade osteogênica de formulações de CP com diferentes proporções de óxido de Nióbio (Nb2O5), substituindo o Bi2O3. Foram utilizados três grupos, um controle e dois experimentais: GC (MTA Angelus®), F6 (75% CP, 20% Nb2O5 e 5% CaSO4) e F7 (75% CP, 10% Bi2O3, 10% Nb2O5e 5% CaSO4). As formulações foram submetidas às análises de Difração de RaioX (DRX), Microscopia Eletrônica de Varredura (MEV), Espectroscopia de Infravermelho com Transformada de Fourier (FTIR), Espectrometria de Fluorescência de Raios-X (FRX), pH, tempo de presa, radiopacidade, resistência a compressão, citotoxicidade e bioatividade. Os dados obtidos foram avaliados estatisticamente pelo teste de variância (ANOVA) com correção de Bonferroni (p<0,05%). O resultado do teste de pH: Nióbio 10% Imediato (12,205 ±0,304); 24h; (12,770 ± 0,226) 48h: (12,910 ± 0,169). Nióbio 20%: imediato (12,080 ± 0,282); 24 h: (12,350 ± 0,593); 48 h: (12,580 ± 0,73). Para o tempo de presa inicial em segundos: MTA (397,500 ±10,606); Nióbio 10% (294,333 + 90,897) e Nióbio 20% (279,000 + 15,874). O tempo de presa final para os grupos foram: MTA (15,000 + 49,497), Nióbio 10% (560 ±38,587), sendo menor quando comparado ao MTA (p<0,001) e Nióbio 20% (715,666 ± 30,664) (p<0,01). Os valores da radiopacidade em mm Al do Nióbio 10% (3,888 ±0,340); Nióbio 20% (3,713 ± 0,712). A resistência a compressão em MPa foi: Nióbio 10% (694,150 + 78,951) Nióbio 20% (699,295 + 47,672). A viabilidade celular não apresentou diferença entre o MTA e grupos experimentais (p<0,05). Os resultados da capacidade osteogênese das formulações a partir do ensaio da fosfatase alcalina (FAL) em UI/L por grama de proteína para cada grupo foi: MTA (1,9 + 1,227) e Nióbio 20% (1,784 + 1,342) (p>0,05). Nossos achados apontam propriedades relevantes para as formulações com Nb2O5 como, pH alcalino, radiopacidade, resistência a compressão e atividade da fosfatase alcalina (AU).
Work aimed to develop, characterize and evaluate the osteogenic activity of PC formulations with different proportions of Niobium oxide (Nb2O5), replacing Bi2O3. Three groups were used, one control and two experimental: GC (MTA Angelus®), F6 (75% CP, 20% Nb2O5 and 5% CaSO4) and F7 (75% CP, 10% Bi2O3, 10% Nb2O5e 5% CaSO4) . The formulations were submitted to X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Fluorescence Spectrometry (FRX), pH, setting, radiopacity, compressive strength, cytotoxicity and bioactivity. The data obtained were statistically evaluated by the test of variance (ANOVA) with Bonferroni correction (p<0.05%). The pH test result: Niobium 10% Immediate (12.205 ±0.304); 24h; (12.770 ± 0.226) 48h: (12.910 ± 0.169). Niobium 20%: immediate (12.080 ± 0.282); 24h: (12.350 ± 0.593); 48 h: (12.580 ± 0.73). For initial setting time in seconds: MTA (397,500 ±10,606); Niobium 10% (294,333 + 90,897) and Niobium 20% (279,000 + 15,874). The final setting time for the groups were: MTA (15,000 + 49,497), Niobium 10% (560 ± 38,587), being smaller when compared to MTA (p<0,001) and Niobium 20% (715,666 ± 30,664) (p<0 .01). Radiopacity values in mm Al of 10% Niobium (3.888 ±0.340); Niobium 20% (3.713 ± 0.712). The compressive strength in MPa was: Niobium 10% (694.150 + 78.951) Niobium 20% (699.295 + 47.672). Cell viability showed no difference between MTA and experimental groups (p<0.05). The results of the osteogenesis capacity of the formulations from the alkaline phosphatase assay (ALF) in IU/L per gram of protein for each group were: MTA (1.9 + 1.227) and Niobium 20% (1.784 + 1.342) (p> 0.05). Our findings point to relevant properties for Nb2O5 formulations such as alkaline pH, radiopacity, compressive strength and alkaline phosphatase activity (AU).
Assuntos
Materiais Biocompatíveis , Cimentos Dentários , Endodontia , Nióbio , Espectrometria de Fluorescência/instrumentação , Microscopia Eletrônica de Varredura , Análise de Variância , Espectroscopia de Infravermelho com Transformada de Fourier , Materiais Dentários , Análise de FourierRESUMO
A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.