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1.
Ars pharm ; 62(1): 40-51, ene.-mar. 2021. tab, graf
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1767

RESUMO

INTRODUCTION: Several natural products exhibit promising antineoplastic activity against bladder cancer cells, including allyl isothiocyanate (AITC). However, the AITC irritates the mucous membranes and induces eczematous or vesicular skin reactions. Thus, pharmaceutical formulations are necessary to overcome these problems. The aim was to develop micellar solutions containing AITC and investigate their antitumoral activity in bladder carcinoma cell lines. METHOD: The micellar solutions were prepared by cold dispersion method. Subsequently, we evaluated cytotoxicity, cell proliferation, cell cycle kinetics and long-term effects of micelles in bladder cancer cells. RESULTS: Cytotoxicity and cell proliferation assays showed there was an increase in AITC activity when it was encapsulated in micelles. We also observed cell cycle arrest in the S phase after treatment with AITC-micelles. Furthermore, the formulation was able to maintain the long-term effects of free AITC. CONCLUSIONS: The micellar solutions developed can become an interesting approach for administration of AITC in the treatment of bladder cancer


INTRODUCCIÓN: Varios productos naturales exhiben actividad antineoplásica prometedora contra las células can¬cerosas de vejiga, incluido el isotiocianato de alilo (AITC). Sin embargo, el AITC irrita las membranas mucosas e induce reacciones cutáneas vesiculares o eccematosas. Por tanto, las formulaciones farmacéuticas son necesarias para superar estos problemas. El objetivo era desarrollar soluciones micelares que contengan AITC e investigar su actividad antitumoral en líneas celulares de carcinoma de vejiga. MÉTODO: Las soluciones micelares se prepararon mediante el método de dispersión en frío. Posteriormente, eval¬uamos la citotoxicidad, la proliferación celular, la cinética del ciclo celular y los efectos a largo plazo de las micelas en las células del cáncer de vejiga. RESULTADOS: Los ensayos de citotoxicidad y proliferación celular mostraron que hubo un aumento en la actividad de AITC cuando se encapsuló en micelas. También observamos la detención del ciclo celular en la fase S después del tratamiento con micelas AITC. Además, la formulación pudo mantener los efectos a largo plazo del AITC libre. CONCLUSIONES: Las soluciones micelares desarrolladas pueden convertirse en un enfoque interesante para la ad¬ministración de AITC en el tratamiento del cáncer de vejiga

2.
Int J Biol Macromol ; 169: 330-341, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33310092

RESUMO

Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCM-DMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.

3.
Nat Prod Res ; : 1-9, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238766

RESUMO

Bladder cancer has a high incidence and recurrence rate among patients worldwide. This study aimed to evaluate the cytotoxic activity of fractions of Sambucus nigra L. flower extracts on bladder carcinoma cells (T24 cells) and human fibroblast cells (MRC-5). The butanolic fraction (F-BuOH) was characterized by UPLC-DAD-MS/MS and nine flavonoids were identified. Rutin was the major compound. The cytotoxic activity of this fraction was observed in the T24 cells but not in MRC-5 cells, indicating selectivity. F-BuOH was incorporated in micellar solutions of Pluronic® F127 and cytotoxic effect for T24 cells was observed again. In vitro assay demonstrated a controlled release of the fraction from the micelles. The results obtained showed that flavonoids are the possible responsible for cytotoxic activity in bladder carcinoma cells. In addition, micellar solutions act together to increase the action of the butanolic fraction.

4.
Mutagenesis ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32789469

RESUMO

The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

5.
Nat Prod Res ; : 1-6, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762451

RESUMO

Ethanolic (EB) extract and hexanic (SH) and hydromethanolic (SEM) sub-extracts of Humulus lupulus leaves were submitted to cytotoxicity evaluation and to phytochemical methods. The effect of EB and SEM on cellular cycle was evaluated by propidium iodide method and the phases were quantified through flow cytometry. The cytotoxicity assessment was done using T24 and MRC5 cells, with EB and SEM (25-1200 µg/mL). By means of UPLC-DAD-MS/MS data were identified the flavonoids astragaline, nicotiflorin, kaempferol-7-O-rutinoside, robinin, hyperin, rutin, quercetin-7-O-rutinoside and manghaslin. EB (800 µg/mL) and SEM (1200 µg/mL) reduces the T24 cell viability. These extracts at 25 µg/mL stimulate the growth of MRC5 cells, evidencing a selective cytotoxicity. After 24 h of the treatment with extracts was not observed cycle arrest of T24 cells. The bioactivity prediction of the flavonoids was evaluated in silico through in house Active-IT software and PASSonline which indicated potential activity as antitumoral, cytotoxic, anti-inflammatory, antiparasitic, antimicrobial, antiviral and others.

6.
Nat Prod Res ; : 1-5, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241181

RESUMO

The aim of this study was to analyse the antitumor effect of the Cymbopogon densiflorus essential oil in silico and in vitro on bladder cancer cells RT4 and T24, with different TP53 status. The oil was extracted by hydrodistillation and the gas chromatography coupled to the mass spectrometry was used for characterisation. In silico analysis was carried out by Pass online software. Cytotoxicity, cell proliferation, cell cycle progression, apoptosis and wound healing assays were performed. Five major compounds were identified. In silico analysis showed that major compounds present high potential for antitumor activities. The treatment with C. densiflorus essential oil reduced cell viability of bladder cancer cells. Only in wild-type cells, the increase of apoptosis rates and the decrease of cell migration were observed. In conclusion, the C. densiflorus essential oil presents antitumor effects on TP53 wild-type and mutated bladder cancer cells, however, the mechanism of action is TP53 status-dependent.

7.
Environ Mol Mutagen ; 61(4): 445-455, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32078183

RESUMO

Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 µM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status. © 2020 Wiley Periodicals, Inc.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Silibina/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
8.
Braz. J. Pharm. Sci. (Online) ; 56: e18411, 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1132049

RESUMO

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

9.
J Nat Prod ; 82(12): 3208-3220, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31815454

RESUMO

The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate their antimicrobial activity. The essential oil was isolated by hydrodistillation from leaves and analyzed by GC-MS. The main constituents were found to be trans-p-mentha-2,8-dien-1-ol, cis-p-mentha-2,8-dien-1-ol, trans-p-mentha-1(7),8-dien-2-ol, cis-piperitol, and cis-p-mentha-1(7),8-dien-2-ol. In silico prediction analysis suggested that this oil possesses antimicrobial potential and the main mechanism of action might be the peptidoglycan glycosyltransferase inhibition. Nanoemulsions were prepared by the phase inversion method, and liposomes were made by the film hydration method. Qualitative evaluation of the antimicrobial activity was performed by the diffusion disk assay with 24 microorganisms; all of them were found to be sensitive to the essential oil. Subsequently, this property was quantified by the serial microdilution technique, where the nanoformulations demonstrated improved activity in comparison with the free oil. Bactericidal action was tested by the propidium iodide method, which revealed that free essential oil and nanoemulsion increased cytoplasmic membrane permeability, while no difference was observed between negative control and liposome. These results were confirmed by images obtained using transmission electron microscopy. This study has shown an optimization in the antimicrobial activity of C. densiflorus essential oil by a nanoemulsion and a liposomal formulation of the active substances.


Assuntos
Anti-Infecciosos/farmacologia , Cymbopogon/química , Nanoestruturas , Óleos Voláteis/farmacologia , Folhas de Planta/química , Animais , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fungos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Concentração de Íons de Hidrogênio , Camundongos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Óleos Voláteis/química , Tamanho da Partícula , Relação Quantitativa Estrutura-Atividade
10.
Nat Prod Res ; : 1-6, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680555

RESUMO

Triplaris gardneriana is used by traditional medicine. The objective of this work was the leaves chemical study with isolate, identify and quantify the chemical constituent, validate the analytical method and evaluate the antibacterial activity. The ethyl acetate and chloroform fractions were subjected to column chromatography for isolation of the compounds quercetin and lupeol, respectively. For the identification, quantification of quercetin in the samples and validation of method were performed using HPLC-DAD. The antibacterial activity was evaluated by the microdilution method. The isolated phytochemicals are being reported for the first time in the species. The ethyl acetate fraction showed a higher content of quercetin with 9.967 ± 1.01 mg.g-1. The method was validated. The samples showed good antibacterial activity. In this study, quercetin was isolated and quantified in the species being a great alternative as a producer of this secondary metabolite, which can be safely applied in the quality control analysis.

11.
Environ Mol Mutagen ; 60(8): 740-751, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31095781

RESUMO

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 µM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Resveratrol/farmacologia , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/genética , Dano ao DNA/genética , Humanos , Antígeno Nuclear de Célula em Proliferação/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular/genética , Proteína Supressora de Tumor p53/biossíntese
12.
Saude e pesqui. (Impr.) ; 12(1): 169-175, jan.-abr. 2019. tab
Artigo em Português | LILACS | ID: biblio-988015

RESUMO

O objetivo deste trabalho foi avaliar o nível de dependência funcional dos idosos com base nas Atividades Básicas da Vida Diária (ABVD) e das Atividades Instrumentais da Vida Diária (AIVD), e investigar o perfil dos idosos e seus cuidadores familiares quanto às características sociodemográficas, econômicas e de saúde. Estudo quantitativo, descritivo e transversal. Realizado na cidade de Vitória de Conquista (BA), com 37 idosos cadastrados no Programa de Atendimento Municipal Domiciliar ao Idoso com Limitação. A coleta dos dados usou o índice de Katz, a escala de Lawton-Brody e um questionário semiestruturado. Predomínio de idosos longevos (51,4%), do gênero feminino (75,7%), e com Hipertensão Arterial (40,5%). Têm dependência moderada (32,4%) para as ABVD, e dependência parcial nas AIVD (81,1%). É razoável afirmar que este resultado apresenta um cenário que se configura em um perfil de vulnerabilidade dos idosos estudados.


Current research evaluates the function dependence of elderly people foregrounded on the Basic Activities of Daily Living (ABVD) and Instrumental Activities of Daily Living (AIVD). Elderly peoples' and caregivers' profiles are also investigated with regard to sociodemographic, economic and health characteristics. Current quantitative, descriptive and transversal study was undertaken in Vitória de Conquista, Brazil, with 37 elderly people enrolled in the Home Care Program with the Elderly with Limitations. Katz index, Lawton-Brody scale and a semi-structured questionnaire were employed. There was a predomination of very aged people (51.4%), females (75.7%), with arterial blood hypertension (40.5%). Moderate dependence (32.4%) for ABVD and partial dependence for AIVD (81.1%). Result presents a scenario of vulnerable profile in the elderly studied.


Assuntos
Idoso , Participação da Comunidade , Tecnologia da Informação , Promoção da Saúde , Saúde do Idoso
13.
Biomed Pharmacother ; 108: 1703-1711, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372873

RESUMO

Chagas disease is a major health problem not only in Latin America but also in Europe and North America due to the spread of this disease into nonendemic areas. In terms of global burden, this major tropical infection is considered to be one of the most neglected diseases, and there are currently only two available chemotherapies: benznidazole and nifurtimox. Unfortunately, although these chemotherapies are beneficial in the acute phase of the disease, benznidazole and nifurtimox lead to significant side effects, including hepatitis and neurotoxicity. Therefore, the search for and development of more effective, safe and inexpensive anti-Trypanosoma cruzi drugs are required. In this work, a series of 10 nitroaromatic Schiff bases bearing different (nitro) aromatic rings-was synthesized. Subsequently, the in vitro and in vivo anti-T. cruzi activities of the Schiff bases were investigated, as well as the in vivo toxicity and the biological effects. The basic structure of the most promising in vivo Schiff base, 10 would be useful in the synthesis of new compounds for Chagas disease treatment.


Assuntos
Hidrocarbonetos Aromáticos/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Testes de Toxicidade , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Administração Oral , Animais , Feminino , Hidrocarbonetos Aromáticos/síntese química , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Parasitemia/tratamento farmacológico , Bases de Schiff/química , Bases de Schiff/toxicidade , Tripanossomicidas/química , Tripanossomicidas/toxicidade
14.
Parasitol Res ; 117(9): 2881-2893, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29943317

RESUMO

Strains of the same Leishmania parasite species, isolated from different host organisms, may exhibit unique infection profiles and induce a change in the expression of microRNAs among host macrophages and in model host mice. MicroRNAs (MiR) are endogenous molecules of about 22 nucleotides that are involved in many regulatory processes, including the vertebrate host immune response. In this respect, the infectivity and susceptibility to antimonials of two L. infantum strains, BH46, isolated from human, and OP46, isolated from symptomatic dog, were characterized in J774 macrophages and BALB/c mice. Parasite burden was assessed in the liver, spleen, and bone marrow using the serial limiting dilution technique. A higher parasite burden was observed in the spleen and bone marrow of animals infected with OP46 compared to BH46 strain. Our results also showed that OP46 was less susceptible to the antimonials. In addition, miR-122 and miR-155 expression was evaluated in the liver and J774 macrophages, and in spleens from infected animals, respectively. An increase was observed in the expression of miR-155 in J774 macrophages infected with both strains compared to uninfected cells, with a higher expression in cells infected with OP46. However, no difference in the expression of miR-122 and miR-155 was observed in the infected animals. Thus, this study shows that OP46 was more infective for mice, it caused a higher increase in miR-155 expression in infected macrophages and was less susceptible to the antimonials evaluated. These data suggest that alteration in miR-155 level likely plays a role in regulating the response to L. infantum.


Assuntos
Tartarato de Antimônio e Potássio/uso terapêutico , Antiparasitários/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Meglumina/uso terapêutico , MicroRNAs/biossíntese , Compostos Organometálicos/uso terapêutico , Animais , Medula Óssea/parasitologia , Modelos Animais de Doenças , Cães , Feminino , Perfilação da Expressão Gênica , Humanos , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Fígado/parasitologia , Macrófagos/parasitologia , Antimoniato de Meglumina , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Carga Parasitária , Baço/parasitologia
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