RESUMO
Croton heliotropiifolius Kunth, popularly known as "velame," is a shrub that resides in northeastern Brazil. The essential oil of C. heliotropiifolius contains high concentrations of volatile compounds in the leaves and is widely used in folk medicine for many purposes as an antiseptic, analgesic, sedative, and anti-inflammatory agent. Due to the apparent limited amount of information, the aim of this study was to determine the cytotoxic potential of essential oil extracted from leaves of C. heliotropiifolius, utilizing different human cancer cell lines (HL-60, leukemia; HCT-116, colon; MDA-MB435, melanoma; SF295, glioblastoma) and comparison to murine fibroblast L929 cell line. The chemical characterization of the essential oil revealed the presence of large amounts of monoterpenes and sesquiterpenes, the majority of which were aristolene (22.43%), germacrene D (11.38%), ɣ-terpinene (10.85%), and limonene (10.21%). The essential oil exerted significant cytotoxicity on all cancer cells, with low activity on murine L929 fibroblasts, independent of disruption of cell membranes evidenced by absence of hemolytic activity. The cytotoxicity identified was associated with oxidative stress, which culminated in mitochondrial respiration dysfunction and direct or indirect DNA damage (strand breaks and oxidative damage), triggering cell death via apoptosis. Our findings suggest that extracts of essential oil of C. Heliotropiifolius may be considered as agents to be used therapeutically in treatment of certain cancers.
Assuntos
Antineoplásicos , Croton , Óleos Voláteis , Sesquiterpenos , Humanos , Animais , Camundongos , Óleos Voláteis/farmacologia , Croton/química , Linhagem Celular Tumoral , Sesquiterpenos/análise , Folhas de Planta/químicaRESUMO
Worldwide, cosmetics (especially eye shadows) are widely consumed and have a great impact on the economy. The aim of this study was to determine the multielement composition, focusing on essential and potentially toxic elements, in cosmetics (eye shadow) exposed to consumption in Brazil. Concentrations of 17 elements (Al, As, Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, Sb, Se, Sr, Ti, V and Zn) were determined in samples (produced in China and Brazil) using a sequential optical emission spectrometer with inductively coupled plasma (ICP OES) after acid digestion, assisted by a closed digester block (6 mL of HNO3 + 2 mL of H2O2 + 1 mL of Triton ×-100 + 1 mL of ultrapure water). The method was validated by linearity, precision, accuracy, limits of detection (LoD) and quantification (LoQ). The elements were quantified (in µg g-1): Al (852-21,900), Ba (3.47-104), Cd (1.70-6.93), Cr (< 8.53-66.6), Cu (< 0.480-14.5), Mn (92.20-1,190), Ni (< 4.23-40.7), Pb (< 2.16-5.06), Sb (1.10-10.5), Sr (0.760-46.0), Ti (32.0-440), V (< 0.85-1.7) and Zn (24.90-2,600). As, Co, Mo and Se in all the investigated samples were found to be below the LoQ values of ICP OES. In this study, regardless of sample compositions and origins (Brazilian or Chinese), high levels of Al, Cd, Cr, Cu, Mn, Ni, Pb, Sb, Ti, V and Zn were observed, exceeding the recommended maximum tolerable limits, according to Brazilian and global legislations, which may present potential risks to human health and the environment.
Assuntos
Oligoelementos , Humanos , Oligoelementos/análise , Brasil , Cádmio , Peróxido de Hidrogênio , ChumboRESUMO
Troxerutin is a natural flavonoid present abundantly in tea, coffee, olives, wheat, and a variety of fruits and vegetables. Due to its diverse pharmacological properties, this flavonoid has aroused interest for treatment of various diseases, and consequently prompted investigation into its toxicological characteristics. The aim of this study was to evaluate the genotoxic and mutagenic effects and chemoprotective activity attributed to troxerutin using human peripheral blood leukocytes (PBLs) through several well-established experimental protocols based upon different parameters. Data demonstrated that troxerutin (100 to 1000 µM) induced no marked cytotoxic effect on PBLs after 24 hr, and did not produce strand breaks and mutagenicity. Regarding chemoprevention, this flavonoid attenuated cytotoxicity, genotoxicity, and mutagenicity initiated by hydrogen peroxide (H2O2) in human PBLs. Further, troxerutin demonstrated no marked cytotoxic effect on PBLs and exerted a protective effect against oxidative stress induced by H2O2 through modulation of GSH-dependent enzymes.
Assuntos
Glutationa/metabolismo , Peróxido de Hidrogênio/farmacologia , Hidroxietilrutosídeo/análogos & derivados , Leucócitos/fisiologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Anticoagulantes/farmacologia , Humanos , Hidroxietilrutosídeo/farmacologia , Leucócitos/efeitos dos fármacos , Leucócitos/enzimologiaRESUMO
The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such as Berberis aquifolium, Berberis vulgaris, Berberis aristata, and Hydrastis canadensis, and of Phellodendron amurense Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistant Candida and Cryptococcus neoformans strains, as well as against the biofilm form of Candida spp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistant Candida and Cryptococcus neoformans strains showed berberine MICs equal to 8 µg/ml and 16 µg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (P < 0.001).
Assuntos
Antifúngicos/farmacologia , Berberina/farmacologia , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/farmacologia , Animais , Berberina/efeitos adversos , Biofilmes/crescimento & desenvolvimento , Candida/classificação , Candida/genética , Candidíase/microbiologia , Linhagem Celular , Proliferação de Células , Criptococose/microbiologia , Cryptococcus neoformans/classificação , Cryptococcus neoformans/genética , DNA Fúngico/genética , Farmacorresistência Fúngica , Fluconazol/efeitos adversos , Humanos , Células L , Camundongos , Testes de Sensibilidade Microbiana , Membranas Mitocondriais/efeitos dos fármacos , Tipagem Molecular , Técnicas de Tipagem MicológicaRESUMO
Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (-)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation.
Assuntos
Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/farmacologia , Fluconazol/farmacologia , Quercetina/farmacologia , Antifúngicos/administração & dosagem , Interações Medicamentosas , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Fluconazol/administração & dosagem , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.
Assuntos
Antineoplásicos , Bufanolídeos , Leucemia , Humanos , Leucócitos Mononucleares , Bromodesoxiuridina/farmacologia , Dano ao DNA , Antineoplásicos/farmacologia , Bufanolídeos/química , Células HL-60 , Apoptose , DNA/farmacologia , Doxorrubicina/farmacologiaRESUMO
There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of Candida tropicalis and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of C. tropicalis that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.
Assuntos
Amiodarona/farmacologia , Antifúngicos/farmacologia , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/patogenicidade , Fluconazol/farmacologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Testes de Sensibilidade MicrobianaRESUMO
Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 µg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains.
Assuntos
Cryptococcus neoformans , Cryptococcus , Humanos , Antifúngicos/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Fluoxetina/farmacologia , Fluconazol/farmacologia , Azóis , Testes de Sensibilidade MicrobianaRESUMO
Hydroxyurea (HU) is the only drug approved for the induction of fetal hemoglobin. Besides this benefit, there are others such as the reduction of leukocyte and generation of nitric oxide (NO). Sickle cell anemia (SCA) is characterized by chronic hemolytic anemia and vaso-occlusive phenomena. The aim of this study was to evaluate the correlation of parameters MDA and NO2 with the prognosis of patients with SCA as outpatients at Hospital Universitário Walter Cantídeo. In all, 65 patients with SCA--51 without the use of HU (group I) and 14 chronically treated with HU (group II)--were recruited. Nitrite and malonaldehyde were determined by biochemical methods. We found that in group II there was a significant difference of serum MDA with clinical variables: two or more transfusions during the year (P<0.0469), the presence of malleolar ulcers (P<0.0400), and the occurrence of vaso-occlusive episodes (P<0.0031), and Group I with the occurrence of three or more vaso-occlusive episodes (P<0.0051). Correlating the malonaldehyde with clinical variables in groups I and II, we observed a statistically significant relationship with two or more transfusions during the year and the presence of malleolar ulcer. Our results demonstrate that MDA levels can be used as parameter for prognosis in SCA.
Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Hidroxiureia/uso terapêutico , Malondialdeído/sangue , Nitritos/sangue , Adulto , Transfusão de Sangue , Brasil , Estudos de Coortes , Feminino , Humanos , Úlcera da Perna/sangue , Estresse Oxidativo , PrognósticoRESUMO
Worldwide, medicinal plants and herbal medicines are widely consumed. The aim of this study was to determine macro- (Ca, K, Mg, Na, and P) and microelements (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se, Si, Sn, Sr, V, and Zn) in medicinal plants and herbal medicines: "globe artichoke" - Cynara scolymus L., "devil's claw" - Harpagophytum procumbens D.C., and "espinheira santa" - Maytenus ilifolia (Mart) ex Reiss. Concentrations of 24 (essential and toxic potentially) elements in samples from Brazil were determined using a sequential optical emission spectrometer with inductively coupled plasma optical emission spectrometry (ICP OES) after acid digestion, assisted by microwave radiation. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to carry out an exploratory analysis of samples. The elements were quantified (in µg/g): Al (20.24-1261.64), Ba (18.90-63.18), Ca (2877.6-19,957.40), Cr (0.28-1.38), Cu (4.16-21.99), Fe (8.54-627.49), K (1786.12-32,297.19), Mg (505.82-6174.52), Mn (0.40-205.64), Na (1717.23-18,596.45), Ni (< LoQ-0.99), P (35.12-2899.91), Se (1.52-3.71), Sn (1.53-12.43), Sr (52.33-84.31), V (< LoQ-0.24), and Zn (2.60-30.56). As, Cd, Co, Mo, Pb, and Sb, in all the investigated samples, were found to be below the limit of detection (LoD) and quantification (LoQ) values of ICP OES. These medicinal plants and herbal medicines can be sources of Ca, K, Mg, Na, P, Cu, Fe, Mn, Se, and Zn. All samples showed considerable levels of Al. PCA and HCA showed that the samples separated into two large groups.
Assuntos
Cynara scolymus , Harpagophytum , Maytenus , Plantas Medicinais , Oligoelementos , Brasil , Análise Espectral , Oligoelementos/análiseRESUMO
This study evaluated the efficacy of potentially probiotic fruit-derived Lactobacillus isolates, namely, L. paracasei 108, L. plantarum 49, and L. fermentum 111, to remove aflatoxin M1 (AFM1) from a phosphate buffer solution (PBS; spiked with 0.15 µg/mL AFM1). The efficacy of examined isolates (approximately 109 cfu/mL) as viable and non-viable cells (heat-killed; 100 °C, 1 h) to remove AFM1 was measured after 1 and 24 h at 37 °C. The recovery of AFM1 bound to bacterial cells after washing with PBS was also evaluated. Levels of AFM1 in PBS were measured with high-performance liquid chromatography. Viable and non-viable cells of all examined isolates were capable of removing AFM1 in PBS with removal percentage values in the range of 73.9-80.0% and 72.9-78.7%, respectively. Viable and non-viable cells of all examined Lactobacillus isolates had similar abilities to remove AFM1. Only L. paracasei 108 showed higher values of AFM1 removal after 24 h for both viable and non-viable cells. Percentage values of recovered AFM1 from viable and non-viable cells after washing were in the range of 13.4-60.6% and 10.9-47.9%, respectively. L. plantarum 49 showed the highest AFM1 retention capacity after washing. L. paracasei 108, L. plantarum 49, and L. fermentum 111 could have potential application to reduce AFM1 to safe levels in foods and feeds. The cell viability of examined isolates was not a pre-requisite for their capacity to remove and retain AFM1.
Assuntos
Aflatoxina M1/química , Lacticaseibacillus paracasei/fisiologia , Lactobacillus plantarum/fisiologia , Limosilactobacillus fermentum/fisiologia , Contaminação de Alimentos , Frutas/microbiologia , Viabilidade Microbiana , ProbióticosRESUMO
Ketamine is a potent uncompetitive NMDA receptor antagonist that provides amnesia, analgesia, environmental dissociation and immobility, where it has its cytotoxic effect well described in the literature. However, the work on its genotoxic/mutagenic potentials are scarce and insufficient and does not allow a reasonable evaluation of its role. Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. Our data revealed that ketamine induces a weak cytotoxic effect on human PBLs after 24â¯h and is devoided of hemolytic effects. A small amount of DNA strand breaks levels were detected in the modified comet assay (employment of FPG enzyme) only at highest concentrations (500 and 700⯵g/mL) of ketamine, highlighting our pro-oxidant data regarding ketamine. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000⯵g/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models.
Assuntos
Anestésicos Dissociativos/toxicidade , Ketamina/toxicidade , Leucócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa , Quebras de DNA , Dano ao DNA , Hemólise/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Estresse OxidativoRESUMO
No carcinogenesis or mutagenesis studies have been carried out with etomidate. The current study showed that etomidate has weak cytotoxic potential after 48 h exposure in human lymphocytes and has no hemolytic activity. The weak cytotoxicity seems to be related with redox imbalance of etomidate (40.9 and 81.9 µM) treated lymphocytes. At both etomidate concentrations, a slight decrease of the levels of GSH intracellular content and a significant increase in the amount of carbonylated proteins were observed after 48 h. The contribution of oxidative stress to genetic toxicity was only perceived when the enzyme Fpg was applied in the comet assay. Etomidate (40.9 and 81.9 µM) is a weak generator of oxidative DNA damage in lymphocytes. These damages to DNA probably were repaired, since no DNA strand breaks were detected in the standard alkaline comet assay (in the presence or absence of hepatic S9 microsomal fraction) without Fpg. Also, no micronucleated lymphocytes or carrying chromosomal aberrations were observed. Finally, etomidate (2046.8 and 4093.5 µM) was not mutagenic in the Salmonella/microsome mutagenicity assay, which used four Salmonella typhimurium strains (TA97a, TA98, TA100, and TA102) to detect frameshift and base-substitution mutations. In summary, etomidate is a weak oxidative DNA damaging anesthetic and is devoid of mutagenic properties in eukaryotic and prokaryotic models.
Assuntos
Etomidato/toxicidade , Hipnóticos e Sedativos/toxicidade , Linfócitos/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Adulto , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Linfócitos/metabolismo , Camundongos , Testes de Mutagenicidade , Salmonella typhimurium/genética , Adulto JovemRESUMO
Introdução: a própolis é uma composição resinosa produzida por abelhas e utilizada em suas colmeias contra microrganismos. Existem diversos tipos desse composto, sendo o de coloração vermelha o último espécime relatado na literatura. Assim, dentre suas aplicabilidades, a atividade antifúngica da própolis vermelha tem sido explorada com vistas a ampliar sua ação terapêutica. Objetivo: explorar estudos acerca da ação antifúngica da própolis vermelha, identificando suas potencialidades e desafios. Metodologia: foi realizada uma revisão integrativa nas bases de dados bibliográficos MEDLINE (via PubMed), SciELO e Google Acadêmico, complementada por uma diligência nas bases de ensaios clínicos ReBEC e Clinical Trials. Em seguida todos os estudos selecionados foram explorados para obtenção do cenário atual sobre o tema. Resultados: foram incluídos 08 estudos, sendo 01 deles um ensaio clínico. Os estudos comprovam a ação antifúngica da própolis vermelha, principalmente contra Candida spp. e Paracoccidioides brasiliensis, e evidenciam a maior potência fungicida deste composto em detrimento de outros tipos de própolis. Conclusão: a ação antifúngica da própolis vermelha mostra-se uma potencialidade em diversos estudos. Entretanto, o volume de pesquisas científicas relativas a esse tema é insuficiente e a complexidade desse composto configura-se como um desafio à sua aplicabilidade.
Introduction: propolis is a resinous composition produced by compounds and used in their hives against microorganisms. There are several types of this compound, the red one is the last specimen reported in the literature. Thus, among its applicability, the antifungal activity of red propolis has been explored as a path to expand its therapeutic action. Objective: to explore studies about the antifungal action of red propolis, identifying its potentialities and challenges. Methodology: Na integrative review was carried out in the bibliographic databases MEDLINE (via PubMed), SciELO and Google Scholar, complemented by a diligence in ReBEC and Clinical Trials databases. Then, all selected studies were explorers to obtain the current scenario on the subject. Results: 08 studies were included, which 01 of them was a clinical trial. Studies prove the antifungal action of red propolis, mainly against Candida spp. and Paracoccidioides brasiliensis, and show the greater fungicidal power of this compound compared to other types of propolis. Conclusion: the antifungal action of red propolis shows potential in several studies. However, the volume of scientific research on this theme is insufficient and the complexity of this compound represents a challenge to its applicability.
Introducción: el propóleo es una composición resinosa producida por las abejas y utilizada en sus colmenas contra los microorganismos. Existen varios tipos de este compuesto, siendo el rojo el último ejemplar reportado en la literatura. Así, entre sus posibilidades de aplicación, se ha explorado la actividad antifúngica del propóleo rojo con vistas a ampliar su acción terapéutica. Objetivo: explorar estudios sobre la acción antifúngica del propóleo rojo, identificando sus potencialidades y desafíos. Metodología: Se realizó una revisión en las bases de datos bibliográficas MEDLINE (vía PubMed), SciELO y Google Scholar, complementada con una diligencia en las bases de datos de ensayos clínicos ReBEC y Clinical Trials. Luego se exploraron todos los estudios seleccionados para obtener el escenario actual sobre el tema. Resultados: Se incluyeron 08 estudios, 01 de los cuales fue un ensayo clínico. Los estudios demuestran la acción antifúngica del propóleo rojo, principalmente contra Candida spp. y Paracoccidioides brasiliensis, y muestran el mayor poder fungicida de este compuesto en detrimento de otros tipos de propóleos. Conclusión: la acción antifúngica del propóleo rojo muestra potencial en varios estudios. Sin embargo, el volumen de investigación científica sobre este tema es insuficiente y la complejidad de este compuesto representa un desafío para su aplicabilidad.
Assuntos
Própole/uso terapêutico , Antifúngicos/uso terapêutico , Paracoccidioides/efeitos dos fármacos , Candida/efeitos dos fármacos , Anti-Infecciosos/uso terapêuticoRESUMO
Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed by an evaluation of their biological activity.
Assuntos
Proliferação de Células/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Animais , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Conformação Molecular , Estrutura Molecular , Compostos Policíclicos/química , Estereoisomerismo , Células Tumorais CultivadasRESUMO
Objectives: The purpose of this study was to evaluate the mutagenic potential of fluoxetine and fluoxetine-galactomannan. Methods: Chromosomal aberration test and Salmonella typhimurium/microsome mutagenicity assay. Results: The results showed that fluoxetine (250 µg/mL) can cause chromosomal breaks of treated leukocytes and increase the frequency of reversion of the tester strains of S. typhimurium / microsome assay only at the highest concentration (5 mg/mL), while fluoxetine encapsulated in galactomannan did not cause these changes (leukocytes and S. typhimuriums strains). Conclusion: In summary, fluoxetine showed a mutagenic effect detectable only at high concentrations in both eukaryotic and prokaryotic models. Furthermore, the fluoxetine/galactomannan complex, in this first moment, prevented the mutagenicity attributed to fluoxetine, emphasizing that the present encapsulation process can be an alternative in preventing these effects in vitro.
Objetivos: avaliar o potencial mutagênico da fluoxetina e da fluoxetina-galactomanana. Métodos: Teste de aberração cromossômica e ensaio de mutagenicidade de Salmonella typhimurium /microssoma. Resultados: a fluoxetina (250 µg/mL) pode causar quebras cromossômicas de leucócitos tratados e aumentar a frequência de reversão das cepas testadoras de S. typhimurium /microssoma apenas na concentração mais alta (5 mg/mL), enquanto a fluoxetina encapsulada em galactomanano não causou essas alterações (leucócitos e cepas de S. typhimurium). Conclusão: a fluoxetina mostrou um efeito mutagênico detectável apenas em altas concentrações em modelos eucarióticos e procarióticos. Além disso, o complexo fluoxetina/galactomanan, neste primeiro momento, evitou a mutagenicidade atribuída à fluoxetina, ressaltando que o presente processo de encapsulamento pode ser uma alternativa na prevenção desses efeitos in vitro.
Assuntos
Fluoxetina , Aberrações Cromossômicas , Salmonella typhimurium , Quebra Cromossômica , Microssomos , Testes de MutagenicidadeRESUMO
We have evaluated the in-vitro and in-vivo antitumour activity of physalin B and physalin D isolated from the aerial parts of Physalis angulata. In-vitro, both compounds displayed considerable cytotoxicity against several cancer cell lines, showing IC50 values in the range of 0.58 to 15.18 microg mL(-1) for physalin B, and 0.28 to 2.43 microg mL(-1) for physalin D. The antitumour activity of both compounds was confirmed in-vivo using mice bearing sarcoma 180 tumour cells. The in-vivo antitumour activity was related to the inhibition of tumour proliferation, as observed by the reduction of Ki67 staining in tumours of treated animals. Histopathological examination of the kidney and liver showed that both organs were affected by physalin treatment, but in a reversible manner. These compounds were probably responsible for the previously described antitumour activity of ethanol extracts of P. angulata, and their identification and characterization presented here could explain the ethnopharmacological use of this species in the treatment of cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lactonas/farmacologia , Sarcoma 180/tratamento farmacológico , Esteroides/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Transplante de Neoplasias , Physalis/química , Sarcoma 180/patologia , Secoesteroides , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the genotoxicity of propolis and L-lysine, as well as their effects on the possible cellular damage in erythroblasts (bone marrow) and leukocytes (peripheral blood) caused by the carcinogen BBN (n - butyl - n {4 - hydroxybutyl} nitrosamine) in rats subjected to bladder carcinogenesis and treated with green propolis and L-lysine. METHODS: One hundred and twenty five rats were distributed into the following groups: I, IIA, IIB, III, K, L M N, X, XI, XII and XIII. Groups I to X received BBN in drinking water for 14 weeks (wks). Group I was treated with intragastric (ig) propolis at 150 mg/kg body weight, for 44 wks, beginning 30 days before start of BBN. Groups IIA and III were treated with propolis (150 mg/kg), for 40 wks, subcutaneous (sc) and ig, respectively, beginning simultaneously with BBN. On the 32nd wk, the animals of groups L, M and N were treated ig with L-lysine (300 mg/kg), celecoxib (30 mg/kg) and propolis (300 mg/kg), respectively, up to the 40th wk. The groups that received only BBN (IIB and K) were treated with water, sc and orally, respectively, for 40 wks. Groups XI, XII and XIII received respectively propolis (150 mg/kg), L-lysine (150 mg/kg) and water ig for 40 wks. After 40 wks, the surviving animals were anesthetized and subjected to femoral bone marrow aspiration and blood collection from the aorta, for CA and MNT, respectively, for investigation of genotoxicity. RESULTS: Groups IIB and K, which received only BBN and water, showed the greatest DNA damage in peripheral leukocytes (CA) and largest number of micronuclei in bone marrow erythrocytes (MNT) in relation to all other groups that received BBN and lysine and/or propolis (p<0.001). CONCLUSIONS: Both propolis and L-lysine are effective in protecting against genotoxicity, as well not being genotoxic themselves toward the cells evaluated, at the doses and times administered and according to the two tests utilized.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Lisina/farmacologia , Própole/farmacologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Animais , Anticarcinógenos/farmacologia , Testes de Carcinogenicidade , Celecoxib , Ensaio Cometa , Dano ao DNA , Testes para Micronúcleos , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/prevenção & controleRESUMO
INTRODUCTION: Amphotericin B (AMB) is an antifungal agent used extensively in clinical medicine, yet resistance remains low. This study aims to evaluate the susceptibility of Candida spp. against AMB. METHODS: For broth microdilution susceptibility testing, 77 strains of Candida spp. were selected (32 C. albicans, 33 C. tropicalis, and 12 C. parapsilosis). The strains were considered susceptible when they exhibited MIC≤1.0µg/ml. RESULTS: None of the strains showed an MIC greater than 0.25µg/ml. CONCLUSIONS: Further works are necessary, with a higher number of strains, to assess the validity of the results used in this study.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/classificação , Humanos , Testes de Sensibilidade MicrobianaRESUMO
O Brasil é um dos países sul-americanos com maior prevalência de acidentes ofídicos por ano, entretanto esses acontecimentos são considerados negligenciados por países tropicais e subtropicais em desenvolvimento. O objetivo deste artigo foi traçar o perfil epidemiológico dos acidentes ofídicos notificados no período 2011-2015, em um Centro de Assistência Toxicológica. Para tanto, fez-se uma pesquisa transversal de abordagem quantitativa realizada com dados epidemiológicos registrados e documentados nas fichas de notificação e de atendimento de acidentes ofídicos. Foram coletadas, para análise, nove variáveis, e os dados encontrados foram analisados por meio de estatística descritiva. Assim, os resultados indicaram a notificação de 183 casos, sendo 19,13% relativos aos acidentes botrópicos. O sexo masculino foi o mais acometido, com 67,76%, e predominou a faixa etária de 10 a 49 anos (73,22%), tendo os membros inferiores como a região anatômica mais afetada (74,32%). A maioria das ocorrências foi na zona rural (54,10%), principalmente agricultores (26,23%), na ocasião em que exerciam sua ocupação (13,66%). Concluiu-se que é necessário o desenvolvimento de pesquisas que contribuam para o (re)conhecimento do perfil epidemiológico desses acidentes como forma de favorecer o desenvolvimento de estratégias preventivas, bem como reforçar a importância da identificação das espécies responsáveis pelos acidentes para que haja um tratamento efetivo e menor risco de ocorrência de óbitos e sequelas nos indivíduos acometidos.
Brazil is one of the South American countries with bigger prevalence of ophidian accidents by year, however these events are considered neglected by tropical and subtropical countries in development process. The objective of this article was to trace the epidemiological profile of ophidian accidents notified from 2011 to 2015 in a Toxicology Assistance Center. For this purpose, a cross-sectional research with quantitative approach was required, carried out with epidemiological data registered and documented to the notification and attention files of snakebite. Nine variables were collected for the research, and data found were analyzed by descriptive statistics. Thus, results indicate the notification of 183 events, 19.13% comprising Bothrops accidents. Male gender was the most affected, with 67,76%, and the age group from 10 to 49 was predominant (73,22%), lower limbs were the most affected body part (74,32%). The majority of the occurrences happened in rural area (54,10), mainly farmers (26,23%), as they were working (13,66%). In conclusion, it's necessary to develop researches that contribute to the (re)cognition of the epidemiological profile of such accidents as a way of favoring the development of preventive strategies, as well as to reinforce the importance of identifying the species responsible for the accidents in order to provide effective treatment and lower the risk of death occurrences and sequels to the individuals affected.
El Brasil es uno de los países sudamericanos con mayor prevalencia de accidentes ofídicos al año, sin embargo estos acontecimientos son considerados descuidados por países tropicales y subtropicales en desarrollo. El objetivo de este artículo fue trazar el perfil epidemiológico de los accidentes ofídicos notificados en el período de 2011 hasta 2015, en un Centro de Asistencia Toxicológica. Para ello, se ha hecho una investigación transversal de abordaje cuantitativo, realizado utilizando datos epidemiológicos registrados y documentados en las fichas de notificación y de atención de accidentes ofídicos. Fueron recogidas para el análisis nueve variables, y los datos encontrados fueron analizados por medio de la estadística descriptiva. Así, los resultados indicaron la notificación de 183 casos, siendo que el 19,13% comprende los accidentes botrópicos. El sexo masculino fue el más acometido, con el 67,76%, y ha predominado el grupo de edad de 10 hasta 49 años (73,22%), teniendo los miembros inferiores como la región anatómica más afectada (74,32%). La mayoría de las ocurrencias fue en la zona rural (54,10%), principalmente agricultores (26,23%), en la ocasión en que ejercían su ocupación (13,66%). Se concluyó que es necesario el desarrollo de investigaciones que contribuyan al (re)conocimiento del perfil epidemiológico de esos accidentes como forma de favorecer el desarrollo de estrategias preventivas, así como reforzar la importancia de la identificación de las especies responsables por los accidentes, para que haya un tratamiento efectivo y un menor riesgo de ocurrencia de muertes y secuelas en los individuos acometidos.