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1.
Braz. J. Pharm. Sci. (Online) ; 55: e18177, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011638

RESUMO

Suspensions of poly ε-caprolactone (PCL) nanoparticles loaded with thyme essential oil were prepared as a natural antioxidant in mayonnaise. Mean particle size was 204.9 ± 2.7 and 240.0 ± 5.5 nm respectively for nanoparticles prepared with PCL alone (NP-C) and for those loaded with thyme essential oil (NP-T). The polydispersity index indicated a homogeneous distribution of all particles, with no significant difference between NP-C and NP-T samples. The nanoparticles showed a large negative charge evidenced by zeta potential rates, indicating high physical stability. The use of PCL as a polymer provided high encapsulation efficiency for thyme essential oil (91.15 ± 2.12 %). DPPH (2,2-diphenyl-1-picrylhydrazyl) method determined IC50 rates were 476.4 ± 33.6 and 483.5 ± 20.4 µg mL-1respectively for unencapsulated oil and for NP-T, evidencing pronounced antioxidant activity. NP-C, NP-T and synthetic antioxidant butylhydroxytoluene (BHT) were applied to samples of mayonnaise and their oxidative stability evaluated for eight days in an oven at 63 ± 3ºC. Results of hydroperoxide value (HP) and thiobarbituric acid reactive substances (TBARS) showed that NP-T had a similar performance as synthetic antioxidant BHT in the prevention of mayonnaise lipid oxidation


Assuntos
Óleos Voláteis/administração & dosagem , Thymus (Planta)/classificação , Oxidação/prevenção & controle , Antioxidantes/efeitos adversos , Hidroxitolueno Butilado/análise , Aromaterapia/métodos , Nanopartículas
2.
São Paulo; s.n; 2015. [156] p. ilus, graf, tab.
Tese em Português | LILACS | ID: biblio-871489

RESUMO

A remodelação do epitélio e do mesênquima subjacente tem um papel crucial na patogênese da fibrose pulmonar experimental. A iniciação, gravidade e distribuição de fibrose varia entre os diferentes agentes químicos. Estudos recentes indicaram que o envolvimento epitelial, a expressão de proteínas reguladoras do epitélio, ativação endotelial, estresse do retículo endoplasmático, a ativação de fibroblastos e acumulação de diferentes tipos de colágeno, pode ser específica em lesão causadas por diferentes agentes químicos. Neste estudo, comparou-se a fibrose pulmonar induzida por bleomicina (BLM) e hidroxitolueno butilado (BHT). Envolvimento epitelial, proteínas reguladoras, ativação endotelial e de fibroblastos foram quantitativamente avaliados pela densidade de células alveolares, expressão de telomerase, endotelina-1 (ET-1), fator de crescimento vascular (VEGF), fator de transformação do crescimento beta (TGF-beta) e do fator de crescimento de fibroblastos básico (bFGF). Estresse celular em células epiteliais alveolares do tipo 2 (AEC II) e fibroblastos, eventualmente, responsáveis pela gênese da fibrose pulmonar, foram investigados por microscopia eletrônica. Os colágenos do tipo I (Col I), III (Col III) e V (Col V) foram caracterizados e quantificados por imunofluorescência. A quantidade de colágeno pulmonar e alterações histológicas fibróticas foram significativamente aumentadas nos grupos BLM e BHT em relação aos controles, com diferença significativa entre a resposta fibrótica precoce e tardia. A densidade AEC II, a expressão da telomerase, ET-1, VEGF, TGF-beta e bFGF foram significativamente maiores nos grupos BLM e BHT do que em pulmões dos grupos controles, com diferença significativa entre a fase precoce e tardia da resposta fibrótica. Mitocôndrias anormais e estresse do retículo endoplasmático em AEC II e fibroblastos foram encontrados em ambos os grupos fibróticos. Aumento no acumulo de fibras de Col I, III e V, foram encontradas no interstício...


Epithelial and underlying mesenchyme remodeling have a critical role in the pathogenesis of experimental pulmonary fibrosis. The initiation, distribution and severity of fibrosis varies among different chemical agents. Recent studies have indicated that epithelial involvement, expression of epithelial regulatory proteins, endothelium activation, endoplasmic reticulum stress, fibroblast activation and accumulation of different types of collagen may be specific in various chemical agents of injury. In this study, bleomycin (BLM) and Butylated hydroxytoluene (BHT)-induced pulmonary fibrosis in mice were compared. Epithelial involvement, regulatory proteins, endothelium and fibroblast activation were quantitatively evaluated by alveolar cells density, telomerase, endothelin-1 (ET-1), Vascular endothelial growth factor (VEGF), Transforming growth factor beta (TGF-beta) and basic fibroblast growth factor (bFGF) expression. Cellular stress in type 2 alveolar epithelial cells (AEC II) and fibroblasts, eventually responsible by generating lung fibrosis, were investigated by electron microscopy. We characterized and quantified collagen type I (Col I), III (Col III) and V (Col V) by immunofluorescence. Lung collagen content and fibrotic histological changes were significantly increased in BLM and BHT models compared to control with significant difference between early and late fibrotic response. AEC II density, telomerase expression, ET-1, VEGF, TGF-beta and bFGF were significantly higher than control lungs with significant difference between early and late BLM and BHT fibrotic response. Abnormal mitochondria and endoplasmic reticulum in AEC II and fibroblasts was found in both groups of chemical agents. Increased of Col I, Col III and V fibers accumulation was found in the lung interstitium after BLM and BHT instillation. The expression of TGF-beta1 and alfa smooth muscle actin (alfa-SMA) gene was significantly increased in both model of pulmonary fibrosis. Activated...


Assuntos
Animais , Masculino , Camundongos , Remodelação das Vias Aéreas , Bleomicina , Hidroxitolueno Butilado , Células Epiteliais , Matriz Extracelular , Fibroblastos , Camundongos , Fibrose Pulmonar , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta
3.
Braz. j. med. biol. res ; 47(7): 567-575, 07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-712970

RESUMO

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.


Assuntos
Animais , Masculino , Apoptose/fisiologia , Colágeno Tipo V/biossíntese , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar/patologia , Telomerase/metabolismo , Hidroxitolueno Butilado , Proliferação de Células , Colágeno Tipo I/análise , Colágeno Tipo II/análise , Colágeno Tipo V/análise , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Imunofluorescência , Fibroblastos/metabolismo , Fibroblastos/patologia , Hidroxiprolina/análise , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Coloração e Rotulagem , Telomerase/isolamento & purificação
4.
Braz. j. pharm. sci ; 48(3): 405-415, July-Sept. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-653454

RESUMO

Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.


Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT foi mais eficiente com relação a estabilidade da sinvastatina e às concentrações mais eficientes para manutenção de estabilidade foram 0,5 e 0,1%. Com relação ao cetoconazol, SMB foi mais eficiente em manter o conteúdo e o perfil de dissolução. A avaliação por DPPH mostrou que o maior percentual de redução de absorção foi observado para PG, enquanto que SMB mostrou ser mais eficiente e consumir menos DPPH. A mesma tendência foi observada com menos eficiência em todos os outros antioxidantes lipofílicos como o BHT e BHA. Os resultados do estudo de modelagem molecular demonstraram que as propriedades eletrônicas obtidas podem ser correlacionadas com a atividade antioxidante em solução, sendo útil para o desenvolvimento racional de formulações farmacêuticas líquidas, mas não para formulações sólidas orais. Este estudo demonstrou a importância de considerar parâmetros de estabilidade e modelagem molecular para elucidar os fenômenos químicos envolvidos na atividade antioxidante, sendo úteis para o uso racional de antioxidantes no desenvolvimento de formulações farmacêuticas.


Assuntos
Administração Oral , Antioxidantes/análise , Uso de Medicamentos/classificação , Preparações Farmacêuticas , Hidroxianisol Butilado/farmacocinética , Hidroxitolueno Butilado/farmacocinética , Cisteína/farmacocinética , Excipientes/classificação , Cetoconazol/análise , Galato de Propila/farmacocinética , Sinvastatina/análise
5.
Genet. mol. biol ; 22(1): 59-64, Mar. 1999. tab
Artigo em Inglês | LILACS | ID: lil-243516

RESUMO

The effect of butylated hydroxytoluene (BHT), a widely used food additive, on chromosomal alterations induced by cadmium chloride (CC) and potassium dichromate (PD) in Chinese hamster ovary (CHO) cells was studied both at metaphase and anaphase-telophase. CHO cells were cultured for 15-16 h in the presence of PD (6.0, 9.0 or 12.0 mM), BHT (1.0 mg/ml), or PD plus BHT as well as CC (0.5, 1.0 and 2.0 mM), BHT or CC plus BHT for the analysis of chromosomal aberrations. To perform the anaphase-telophase test, cells were cultured in cover glasses and treated 8 h before fixation with the same chemicals. An extra dose of CC (4 mM) was used in this test. Both metal salts significantly increased chromosomal aberration frequencies in relation to untreated controls, and to DMSO- and BHT-treated cells. Post-treatment with BHT decreased the yield of chromosomal damage in relation to treatments performed with CC and PD. However, chromosomal aberration frequencies were significantly higher than those of the controls. In the anaphase-telophase test, CC significantly increased the yield of lagging chromosomes with the four doses employed and the frequency of lagging fragments with the highest dose. In combined treatments of CC and BHT, frequencies of the two types of alterations decreased significantly in relation to the cells treated with CC alone. No significant variation was found in the frequencies of chromatin bridges. Significant increases of numbers of chromatin bridges, lagging chromosomes and lagging fragments were found in cells treated with PD. The protective effect of BHT in combined treatments was evidenced by the significant decrease of chromatid bridges and lagging chromosomes in relation to PD-treated cells. Whereas BHT is able to induce chromosomal damage, it can also protect against oxidative damage induced by other genotoxicants.


Assuntos
Animais , Cricetinae , Anti-Infecciosos Locais/farmacologia , Antioxidantes/farmacologia , Hidroxitolueno Butilado/farmacologia , Aberrações Cromossômicas , Cromossomos/efeitos dos fármacos , Cloreto de Cádmio/farmacologia , Dicromato de Potássio/farmacologia , Mutagênicos/farmacologia , Ovário/citologia , Cricetulus
6.
Arch. med. res ; 27(1): 71-5, 1996. tab
Artigo em Inglês | LILACS | ID: lil-200294

RESUMO

We previously reported on the induction by vitamin A of gallstones, rich in calcium and phosphate, in hamsters. On the other hand, it has been reported that the phenolic antioxidant butylate hydroxytoluene (BHT) potentiates the hepatotoxicity of vitamin A. In the present work we have tested the effect of BHT on the lithogenicity of vitamin A and on bile composition. The urinary excretion of calcium and phosphate was determined to assess a possible asymptomatic bone resorptin due to vitamin A toxicity, and/or an effect of BHT on the homeostasis of calcium and phosphate. Theree groups of 18 male hamsters were fed with the following diets for 70 days: Group 1, Purina Nutricubes (DB); Group 2, DB + 25,000 IU percent retinol acetate (DL); group 3, DL + 500 mg percent BHT. Vitamin A (group 2) induced gallstones in 78 percent of the animals, increased bile flow and biliary phosphate and calcium concentrations, and reduced those of bili salt, cholesterol and phospholipid. BHT (Group 3) reduced gallstone frequency to 5.5 percent, and decreased biliary phosphate, calcium and lipids toward more normal concentrations. Vitamin A alone or with BHT did not significantly affect food intake or urinary excretion of calcium and phosphate


Assuntos
Cricetinae , Animais , Masculino , Anestesia Geral/veterinária , Hidroxitolueno Butilado/uso terapêutico , Cálcio/metabolismo , Cálculos/induzido quimicamente , Colelitíase/induzido quimicamente , Cricetinae/metabolismo , Hepatopatias/induzido quimicamente , Pentobarbital , Fosfatos/metabolismo , Vitamina A/toxicidade
7.
Rev. cuba. aliment. nutr ; 4(2): 198-203, mayo-ago. 1990. tab
Artigo em Espanhol | LILACS | ID: lil-91486

RESUMO

Se ensayó un método de análisis para determinar los contenidos de butilhidroxianisol (BHA) y butilhidroxitolueno (BHT) en alimentos, basado en la extracción con alcohol metílico en una columna que contiene sulfato de sodio anhidro, evaporación del extracto, dilución del residuo con éter etilico e inyección en un cromatógrafo de gases equipado con un detector de ionización de llama. La precisión y la exactitud obtenidas fueron aceptables. El método es útil para investigaciones y para el control sanitario de estos aditivos


Assuntos
Hidroxianisol Butilado/análise , Hidroxitolueno Butilado/análise , Cromatografia Gasosa , Análise de Alimentos
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