Antitumoral activity of micellar solutions containing allyl isothiocyanate: an in vitro study / Actividad antitumoral de soluciones micelares que contienen isotiocianato de alilo: un estudio in vitro

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

The activation of the Nrf2/ARE pathway in HepG2 hepatoma cells by phytochemicals and subsequent modulation of phase II and antioxidant enzyme expression

Previous studies have shown that naturally occurring phytochemicals, indole-3-carbinol, phenethyl isothiocyanate, protocatechuic acid, and tannic acid increased the activity and protein level of hepatic phase II enzymes in animal models. In order to further explore the mechanism of this activity, we investigated the effect of these compounds on the activation of nuclear factor erythroid-2-related factor 2 (Nrf2)-regulated transcription in human hepatocellular carcinoma HepG2 cells. Treatment with all the tested compounds resulted in the translocation from the cytosol and nuclear accumulation of active phosphorylated Nrf2. Furthermore, phenethyl isothiocyanate and indole-3-carbinol increased the transcript and protein levels of GSTA, GSTP, GSTM, GSTT, and NQO1. On the other hand, protocatechuic and tannic acids enhanced only the expression of GSTA, GSTM, and GSTT. The expression of genes encoding antioxidant enzymes CAT, SOD, GR, and GPx was increased after the treatment with all the tested phytochemicals. These results indicate that isothiocyanates/indoles and protocatechuic and tannic acids induce phase II and antioxidant gene expression in HepG2 cells through the Nrf2-Keap1-ARE signaling pathway. Moreover, the results of this study confirmed that the degradation products of glucosinolates are more effective inducers of phase II and antioxidant enzymes than protocatechuic and tannic acids

Clinical and molecular evidence of the consumption of broccoli, glucoraphanin and sulforaphane in humans / Evidencias clínicas y moleculares del consumo de brócoli, glucorafanina y sulforafano en humanos

Introduction: Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin (GRA), which is found in great amounts especially in broccoli. Its consumption has been reported to be associated with a lower risk of myocardial infarction and cancer development. Additionally, its effects have been studied in neurodegenerative diseases, diabetes, and atherosclerosis, most of the times using animal models and cell cultures. Objectives: Given the promising results of SFN, this review aimed to investigate evidence documented in human intervention studies with broccoli, GRA and SFN. Methods: A search was performed on PubMed and Virtual Health Library databases by two independent researchers using the descriptors 'broccoli' or 'glucoraphanin' or 'sulforaphane', which should appear on the study’s title or abstract. This review included randomized linical trials performed in humans that were published in English and Portuguese from 2003 to 2013 and that considered clinical and molecular parameters of cell damage as outcomes of interest. Results: Seventeen studies were selected, and the predominant type of intervention was broccoli sprouts. More consistent results were obtained for the clinical parameters blood glucose and lipid profile and for molecular parameters of oxidative stress, indicating that there was an improvement in these parameters after intervention. Less solid evidence was found with regard to decreased inflammation, Helicobacter pylori colonization, and protection against cancer. Conclusion: Although being relevant, the evidence for the use of broccoli, GRA and SFN in humans are limited; Introduction: Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin (GRA), which is found in great amounts especially in broccoli. Its consumption has been reported to be associated with a lower risk of myocardial infarction and cancer development. Additionally, its effects have been studied in neurodegenerative diseases, diabetes, and atherosclerosis, most of the times using animal models and cell cultures. Objectives: Given the promising results of SFN, this reviewaimed to investigate evidence documented in human intervention studies with broccoli, GRA and SFN. Methods: A search was performed on PubMed and Virtual Health Library databases by two independent researchers using the descriptors 'broccoli' or 'glucoraphanin' or 'sulforaphane', which should appear on the study’s title or abstract. This review included randomized clinical trials performed in humans that were published in English and Portuguese from 2003 to 2013 and that considered clinical and molecular parameters of cell damage as outcomes of interest. Results: Seventeen studies were selected, and the predominanttype of intervention was broccoli sprouts. More consistent results were obtained for the clinical parameters blood glucose and lipid profile and for molecular parameters of oxidative stress, indicating that there wasan improvement in these parameters after intervention. Less solid evidence was found with regard to decreased inflammation, Helicobacter pylori colonization, and protection against cancer. Conclusion: Although being relevant, the evidence for the use of broccoli, GRA and SFN in humans are limited thus, further intervention studies are needed to evaluate outcomes more consistently and reach better grounded conclusions (AU)

Introducción: El sulforafano (SFN) es un isotiocianato derivado de la glucorafanina (GRA), encontrada en gran cantidad especialmente en el brócolis. Su consumo está asociado a un menor riesgo de infarto del miocardio y de cáncer. Además, sus efectos están siendo estudiados en enfermedades neurodegenerativas, diabetes y aterosclerosis, casi siempre utilizando modelos animales y cultivos celulares. Objetivos: Debido a los resultados prometedores del compuesto SFN, esta revisión buscó investigar evidencias ya documentadas en intervenciones con brócoli, GRA y SFN en humanos. Métodos: Se realizó una búsqueda en las bases de datos PubMed y Biblioteca Virtual en Salud, por dos investigadores independientes, utilizando los descriptores 'broccoli' o 'glucoraphanin' o 'sulforaphane', que debían constar en el título o resumen del trabajo. Se incluyeron ensayos clínicos randomizados realizados en humanos, publicados en inglés y portugués entre 2003 y 2013, y que consideraron como desenlaces de interés parámetros clínicos y moleculares de daño celular. Resultados: Se seleccionaron 17 estudios y el tipo de intervención predominante fueron brotes de brócoli. Los resultados más consistentes fueron obtenidos con los parámetros clínicos glicemia y perfil lipídico y los parámetros moleculares de estrés oxidativo, que presentaron mejora después de la intervención. Se encontraron evidencias menos sólidas respeto a la disminución de la inflamación, de la colonización por Helicobacter pylori y protección contra cáncer. Conclusión: Aunque relevantes, las evidencias del uso Correspondence: Carolina Guerini de Souza. de brócoli, GRA y SFN en humanos son limitadas, siendo necesarios más estudios de intervención para avaluar los desenlaces de forma más consistente y producir conclusiones mejor fundamentadas (AU)

Local ciliate communities associated with aquatic macrophytes

This study, based within the catchment area of the River Frome, an important chalk stream in the south of England, compared ciliated protozoan communities associated with three species of aquatic macrophyte common to lotic habitats: Ranunculus penicillatus subsp. pseudofluitans, Nasturtium officinale and Sparganium emersum. A total of 77 ciliate species were counted. No species-specific ciliate assemblage was found to be typical of any one plant species. Ciliate abundance between plant species was determined to be significantly different. The ciliate communities from each plant species were unique in that the number of species increased with ciliate abundance. The community associated with R. penicillatus subsp. pseudofluitans showed the highest consistency and species richness whereas S. emersum ciliate communities were unstable. Most notably, N. officinale was associated with low ciliate abundances and an apparent reduction in biofilm formation, discussed herein in relation to the plant’s production of the microbial toxin phenethyl isothiocyanate. We propose that the results reflect differences in the quantity and quality of biofilm present on the plants, which could be determined by the different plant morphologies, patterns of plant decay and herbivore defense systems, all of which suppress or promote the various conditions for biofilm growth (AU)

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Benzyl isothiocyanate disturbs lipid metabolism in rats in a way independent of its thyroid impact following in vivo long-term treatment and in vitro adipocytes studies

During recent decades, benzyl isothiocyanate (BITC) was examined mainly in terms of its cancer chemopreventive action. Although some research has been conducted on goitrogenic activity of many glucosinolate derivatives, little attention has been paid to the BITC impact on the thyroid gland and lipid metabolism strictly associated with it. Therefore, this research project aimed at expanding our knowledge about how non-physiological doses of BITC (widely used in chemotherapy) influence some hormonal and metabolic (lipid) parameters in in vivo and in vitro experiments. The trial was focused on BITC action on thyroid tissue, liver, as well as white adipocyte tissue, at doses which were previously proved to exert a strong anticancer effect (10 mg/kg body weight in vivo and 1, 10 and 100 μmol/L in in vitro trials, respectively). Two-week oral administration of BITC in in vivo trial affected thyroid gland by decreasing total thyroxine and triiodothyronine. However, the obtained lipid profile was not specific for thyroid hormone deficiency because no lipid changes in the blood serum and liver steatosis were observed. BITC per se evoked elevation of basal lipolysis at 1 and 100 μmol/L and limitation of basal lipogenesis at 100 μmol/L in adipocyte tissues in in vitro experiment. BITC did not remain indifferent to liver metabolism by its possible influence on hepatic cholesterol 7α-hydroxylase and 5-deiodinase as well as on adipocytes by its enhanced basal lipolysis and limited lipogenesis independently of epinephrine and insulin action steps, respectively. Additionally, BITC was probably involved in bile flow obstruction

Propiedades químicas, biológicas y valor nutritivo del licopeno / Chemical and biological properties and nutritional value of lycopene

Las dietas ricas en alimentos de origen vegetal, con gran variedad de sustancias fitoquímicas de distinta naturaleza (flavonoides, carotenoides, monoterpenos, isotiocianatos y fitoesteroles), se han asociado con numerosos efectos beneficiosos para la salud. Los carotenoides son pigmentos naturales sintetizados por las plantas y microorganimos, y aunque su importancia se ha centrado en aquéllos que poseen actividad vitamina A, en la actualidad otros carotenoides como el licopeno, están despertando interés por sus propiedades biológicas. El licopeno se encuentra en nuestra dieta formando parte de los carotenos del tomate, sandía, papaya, albaricoque y pomelo rosa, debiéndose destacar que el tomate y sus productos procesados son los que intervienen en mayor medida a su ingesta. Los efectos beneficiosos del licopeno se derivan de la capacidad de secuestrar radicales libres, siéndo además este efecto superior al detectado en otros carotenoides, tanto in vitro como in vivo. Los distintos estudios epidemiológicos relacionan al licopeno con la prevención de enfermedades cardiovasculares y de determinados procesos cancerígenos, principalmente a nivel de tejidos epiteliales. El presente trabajo de revisión tiene como objetivo compilar la importancia del licopeno en la dieta, sus propiedades químicas y biológicas, y sus efectos fisiológicos beneficiosos, destacando los aspectos más importantes relacionados con su presencia en el tomate. (AU)

Importancia de los marcadores serológicos en el diagnóstico de la enfermedad celíaca / Serological markers of coeliac disease

En este artículo se revisa la sensibilidad y especificidad de los diferentes marcadores serológicos de enfermedad celíaca: anticuerpos antigliadina, antiendomisio, antirreticulina y antitransglutaminasa tisular. La meta continúa siendo el desarrollo de un test que pueda reemplazar a la biopsia intestinal en el diagnóstico de la enfermedad celíaca (AU)