Xanthatin and 8-epi-xanthatin as new potential colchicine binding site inhibitors: a computational study.

CONTEXT: Phytocompounds xanthatin and 8-epi-xanthatin, obtained from Xanthium chinese Mill, showed antitumoral activity in vitro related to the microtubules destabilizing properties of these phytocompounds. Five binding sites for microtubule destabilizing agents have been characterized on tubulin by high-resolution X-ray crystallography: vinca domain, colchicine, pironetin, maytansine site, and more recently, the seventh site. This work aims to develop a comprehensive computational strategy to understand and eventually predict the interaction between xanthatin and 8-epi-xanthatin with the destabilizing-antimitotic binding domain of the tubulin heterodimer. In addition, we propose a putative binding site for these phytocompounds into the microtubule destabilizing binding sites on the tubulin heterodimer. Xanthanolides showed higher stability in the colchicine and pironetin binding sites, whit a greater affinity for the former. In addition, we found that xanthanolides and non-classical colchicine binding site inhibitors share a high structural similarity. METHODS: The 3D structures for xanthatin and 8-epi-xanthatin were obtained using DFT with the hybrid functional B3LYP and the base 6-31G (d,p), implemented in Gaussian 09. The 3D coordinates for tubulin proteins were downloaded from PDB. The complexes tubulin-xanthanolides were predicted using a Monte-Carlo iterated search combined with the BFGS gradient-based optimizer implemented in the AutoDock Vina. The xanthanolides-tubulin complexes were energy minimized by molecular dynamics simulations at vacuum, and their stabilities were evaluated by solvated molecular dynamics simulations during 100 ns. All molecular dynamics simulations were performed using the conjugate gradient method implemented in NAMD2 and CHARMM36 forcefield.

Synthesis of Four Steroidal Carbamates with Antitumor Activity against Mouse Colon Carcinoma CT26WT Cells: In Vitro and In Silico Evidence.

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.

Antigenotoxic, antiproliferative and antimetastatic properties of a combination of native medicinal plants from Argentina.

ETHNOPHARMACOLOGICAL RELEVANCE: Jarilla is the common name of an appreciated group of native plants from the semi-arid region in Argentina (Larrea cuneifolia Cav., Larrea divaricata Cav. and Zuccagnia punctata Cav.) that have been historically consumed to heal respiratory, musculoskeletal and skin ailments, as well as recommended for weakness/tiredness, hypertension, diabetes and cancer treatment. It was previously reported that some biological properties could be improved when these plants are used jointly. Infusions of a defined mixture, composed by three Jarilla species, L. cuneifolia: L. divaricata: Z. punctata (0.5:0.25:0.25) (HM2) showed synergistic and additive effect on antioxidant activity even after passing through the gastro-duodenal tract. AIM OF THE STUDY: The main purpose of this work was to evaluate antigenotoxic, antitumor, and anti-metastatic properties of the Jarilla species that grow in the Northwest of Argentina and a herbal combination of them. MATERIAL AND METHODS: Infusions of Jarilla mixture (HM2), and of each single plant species were prepared. Phenolic profiles of infusions were analyzed by HPLC-ESI-MS/MS and two relevant chemical markers were quantified. The antigenotoxic activity was evaluated by using the Ames test and the Cytokinesis-Block Micronucleus (CBMN) assay against direct mutagens. Evaluations of both cytotoxicity and antiproliferative effects were conducted on tumor and non-tumor cell lines. Both in vivo tumoral growth and metastasis inhibition were evaluated by using a carcinoma model on Balb/c mice. RESULTS: HM2 mix could suppress genetic and chromosome mutations induced by 4-nitro-o-phenylendiamine (4-NPD) and doxorubicin. Herbal mixture and single plant infusions showed cytotoxic effect against mammary, uterus, and brain tumoral cells without a selective action vs normal human cell line. HM2 mix was able to reduce mammary tumor mass on the Balb/c mice model and showed a significant reduction in the number of metastatic nodules in the lungs. CONCLUSIONS: Our results suggest that the combinations of three Jarilla species from northwest Argentina would be a promising alternative to treat or slow down the development of chronic diseases, such as cancer.

Targeting Ovarian Cancer Cell Cytotoxic Drug Resistance Phenotype with Xanthium strumarium L. Extract.

Emerging drugs aim at targeting the genomic integrity and replication machinery in ovarian cancer. While the antiproliferative activity of Xanthium strumarium L. extract (XFC), a traditional herbal medicine, is believed to alter the mitotic apparatus of Chinese hamster ovary epithelial cells, its capacity to target and overcome the chemoresistance phenotype in ovarian cancer is unknown. Among the cancer cell lines tested, we found that the best proliferation inhibitory effect for XFC was against ovarian cancer cells and ranged from 30 to 35 µg/mL. XFC efficiently targeted both the cytotoxic drug chemoresistance phenotype of SKOV-3 cells and of the chemosensitive ES-2 cells. Early apoptosis and late apoptosis were effectively induced by XFC extract in ES-2 cells, whereas late apoptosis and necrosis events were triggered in SKOV-3 cells. Cell cycling regulation was trapped by XFC extract in the G2/M phase in both the ES-2 and SKOV-3 cell models. This effect was, in part, attributable to increased dose-dependent tubulin polymerization, which was increased in SKOV-3 cells. Whereas XFC extract triggered poly (ADP-Ribose) polymerase (PARP) cleavage in both ES-2 and SKOV-3 cells, it only lowered Nrf2 in ES-2 cells and phosphorylated Akt levels in SKOV-3 cells. Interestingly, cell cycling regulators Cdk4, Cyclin D3, and p27 were all decreased in SKOV-3 cells. XFC extracts were effective in inhibiting in vitro migration in both ovarian cancer cell models. Our data support the potential anticancer targeting of chemoresistant human ovarian cancer cells phenotype by XFC extract.

Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. We previously reported that Xanthium strumarium L. induces mitotic arrest in proliferating cells, a process mediated by xanthatins. HYPOTHESIS/AIM: The aim of this work is to study if xanthatins, isolated from X. strumarium total extract, affect the proliferative capacity of CT26WT colon cancer cells and, in consequence, if tumor growth and proliferation of (lung) metastatic sites can also be arrested in vivo. STUDY DESIGN: This study consisted of both in vitro and in vivo experiments involving the CT26WT cell line and a subcutaneous mouse model of colon cancer. In vitro cell cycle progression, in vivo tumoral growth and anti-metastatic activity were analyzed to investigate whether xanthatins of X. strumarium induce mitotic arrest in proliferating colorectal carcinoma. RESULTS: Our in vitro results show that X. strumarium, mediated by xanthatins, induces G2/M arrest and impair anaphase entrance. This leads to a significant induction of apoptotic and necrotic in CT26WT cells, demonstrating their significant anti-proliferative activity through interfering with the mitotic apparatus. Furthermore, our in vivoresults reveal that X. strumarium inhibits both tumor growth and metastasis progression. CONCLUSION: X. strumarium antitumor activities are mainly mediated by xanthatins through inhibition of tumor growth and metastasis, inducing mitotic arrest and apoptosis in colon carcinoma cells. These findings further confirm the therapeutic potential of X. strumarium in colorectal cancer.

Xanthium strumarium extract inhibits mammalian cell proliferation through mitotic spindle disruption mediated by xanthatin.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium strumarium L. is a member of the Asteraceae family popularly used with multiple therapeutic purposes. Whole extracts of this plant have shown anti-mitotic activity in vitro suggesting that some components could induce mitotic arrest in proliferating cells. AIM OF THE SUDY: Aim of the present work was to characterize the anti-mitotic properties of the X. strumarium whole extract and to isolate and purify active molecule(s). MATERIALS AND METHODS: The capacity of the whole extract to inhibit mitotic progression in mammalian cultured cells was investigated to identify its anti-mitotic activity. Isolation of active component(s) was performed using a bioassay-guided multistep separation procedure in which whole extract was submitted to a progressive process of fractionation and fractions were challenged for their anti-mitotic activity. RESULTS: Our results show for the first time that X. strumarium whole extract inhibits assembly of the mitotic spindle and spindle-pole separation, thereby heavily affecting mitosis, impairing the metaphase to anaphase transition and inducing apoptosis. The purification procedure led to a fraction with an anti-mitotic activity comparable to that of the whole extract. Chemical analysis of this fraction showed that its major component was xanthatin. CONCLUSIONS: The present work shows a new activity of X. strumarium extract, i.e. the alteration of the mitotic apparatus in cultured cells that may be responsible for the anti-proliferative activity of the extract. Anti-mitotic activity is shown to be mainly exerted by xanthatin.

Xanthium strumarium L. extracts produce DNA damage mediated by cytotoxicity in in vitro assays but does not induce micronucleus in mice.

Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25-100 µg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations.

Search of new Antimitotics compounds from the Cuban flora / Búsqueda de nuevos compuestos con actividad antimitótica en la flora cubana

The main objective of anti-carcinogenic chemotherapy is to stop uncontrolled cellular proliferation. This has prompted us to begin a systematic survey of new effective inhibitors with ability to react with cytoskeletal components and arrest living, dividing cells. Even for traditional populations herbs-consuming, encouraging the use of species with chemopreventive actions could be helpful as part of life expectancy improvement strategies. Herbal products have significantly lower costs, exhibit little or no toxicity during long-term oral administration and are relatively available at large scale. Current work involved the screening of 85 extracts from Cuban medicinal plants, selected on the basis of traditional use, ethnobotanics and pharmacological information (antiparasitic, antitumour, abortive, etc.). Antitubulinic activity in the hydroalcoholics extracts was evaluated by using a modified version of the conventional turbidity assay of tubulin assembly/ disassembly. The activity limits of the news isolated antitubulin agents were thoroughly investigated. According to the presented results, the extracts displaying the highest antitubulinic activity were Tamarindus indica L., Lawsonia inermes L and Xanthium strumarium L.

Detener la proliferación celular es el principal propósito de la quimioterapia anticarcinogénica. Para ello se ha realizado una búsqueda a partir de fuentes naturales de nuevos inhibidores efectivos que reaccionen con los componentes del citoesqueleto y puedan detener la división celular. En poblaciones que tradicionalmente utilizan plantas medicinales se estimula el uso de aquellas especies con acción quimiopreventivas como parte de una estrategia que contribuya a la calidad de vida. Los productos herbarios tienen costos significativamente más bajos, exhiben poca o ninguna toxicidad durante la administración oral a largo plazo y están al alcance de todos. Nuestro trabajo consistió en realizar un tamizaje de 85 extractos de plantas medicinales cubanas seleccionadas en base al uso tradicional, en las encuestas etnobotánicas e información farmacológica (actividad antiparasitaria, antitumoral, abortiva, etc). La actividad antitubulínica fue evaluada mediante una versión modificada del ensayo turbimétrico del ensamblaje/desensamblaje de la tubulina. Se determinó la actividad límite de los nuevos agentes antitubulínicos siendo los extractos de Tamarindus indica L., Lawsonia inermes L and Xanthium strumarium L. los de mejor actividad antitubulínica según las condiciones ensayadas.

Genotoxicidad de Justicia pectoralis Jacq: (tilo) / Genotocixity of Justicia pectoralis Jacq: (tilo)

Objetivo: determinar el efecto genotóxico del extracto hidroalcohólico 30 por ciento de partes aéreas de Justicia pectoralis Jacq. (variedad pectoralis) secado por spray dryer. Métodos: se empleó el ensayo Salmonella/microsomas con las líneas TA 1535, TA 1537, TA 98 y TA 100 con un rango de concentraciones de 50 a 5 000 mg de polvo/placa (± S9) según el protocolo de incorporación en placas; para el ensayo de micronúcleos en médula ósea se utilizaron ratones Cenp: NMRI de los 2 sexos, que recibieron dosis isovolumétricas (10 mL/kg) de 500, 1 000 y 2 000 mg de polvo/kg, por vía intragástrica, separadas 24 h, con sacrificio 24 h después de la última aplicación. Resultados: no se encontró efecto genotóxico con ninguna de las cepas en el ensayo de Salmonella/microsomas y el extracto no causó un aumento estadísticamente significativo en la frecuencia de eritrocitos policromáticos micronucleados en los ratones tratados y no mostró relación dosis respuesta positiva. Conclusiones: el polvo no reveló efecto genotóxico en las condiciones experimentales de este estudio(AU)

Objective: to detemine the genotoxic effect of the hydroalcoholic extract 30 % of aerial parts of Justicia pectoralis Jacq. (variety pectoralis) dried by spray drier. Methods: the Salmonella/microsomes with lines TA 1535, TA 1537, TA 98 and TA 100 with a concentration range from 50 to 5 000 ìg of powder/plaque (± S9) was used according to the protocol of incorporation in plaques; for the bone marrow micronucleus assay there were used Cenp mice: NMRI of both sexes that received isovolumetric doses (10 mL/kg) of 500, 1 000 y 2 000 mg of powder/kg by intragastric route at intervals of 24 h and were sacrificed 24 h after the last application. Results: no genotoxic effect was found with any of the strains in the assay of Salmonella/microsomes. The extract did not cause a statistically significant increase in the frequency of micronucleated polychromatic erythrocytes in the mice treated. No dose/positive response relation was observed. Conclusions: the powder did not reveal genotoxic effect under the experimental conditions of this(AU)

Genotoxicidad de Justicia pectoralis Jacq: (tilo) / Genotocixity of Justicia pectoralis Jacq: (tilo)

Objetivo: determinar el efecto genotóxico del extracto hidroalcohólico 30 por ciento de partes aéreas de Justicia pectoralis Jacq. (variedad pectoralis) secado por spray dryer. Métodos: se empleó el ensayo Salmonella/microsomas con las líneas TA 1535, TA 1537, TA 98 y TA 100 con un rango de concentraciones de 50 a 5 000 mg de polvo/placa (± S9) según el protocolo de incorporación en placas; para el ensayo de micronúcleos en médula ósea se utilizaron ratones Cenp: NMRI de los 2 sexos, que recibieron dosis isovolumétricas (10 mL/kg) de 500, 1 000 y 2 000 mg de polvo/kg, por vía intragástrica, separadas 24 h, con sacrificio 24 h después de la última aplicación. Resultados: no se encontró efecto genotóxico con ninguna de las cepas en el ensayo de Salmonella/microsomas y el extracto no causó un aumento estadísticamente significativo en la frecuencia de eritrocitos policromáticos micronucleados en los ratones tratados y no mostró relación dosis respuesta positiva. Conclusiones: el polvo no reveló efecto genotóxico en las condiciones experimentales de este estudio.

Objective: to detemine the genotoxic effect of the hydroalcoholic extract 30 of aerial parts of Justicia pectoralis Jacq. (variety pectoralis) dried by spray drier. Methods: the Salmonella/microsomes with lines TA 1535, TA 1537, TA 98 and TA 100 with a concentration range from 50 to 5 000 ìg of powder/plaque (± S9) was used according to the protocol of incorporation in plaques; for the bone marrow micronucleus assay there were used Cenp mice: NMRI of both sexes that received isovolumetric doses (10 mL/kg) of 500, 1 000 y 2 000 mg of powder/kg by intragastric route at intervals of 24 h and were sacrificed 24 h after the last application. Results: no genotoxic effect was found with any of the strains in the assay of Salmonella/microsomes. The extract did not cause a statistically significant increase in the frequency of micronucleated polychromatic erythrocytes in the mice treated. No dose/positive response relation was observed. Conclusions: the powder did not reveal genotoxic effect under the experimental conditions of this.

Genotoxicidad de Indigofera suffruticosa Mill / Genotocixity of Indigofera suffruticosa Mill

Se estudió el efecto genotóxico de un extracto de Indigofera suffruticosa Mill. mediante el ensayo Salmonella/microsomas con las líneas TA 1535, TA 1537, TA 98 y TA 100 que resultó positivo para el protocolo de incorporación en placas con las cepas TA 1535, TA 1537 con un rango de concentraciones de 50 a 5000 µg/placa (±S9). Mediante el ensayo de inducción de micronúcleos en médula ósea de ratón el extracto exhibió un aumento estadísticamente significativo en la frecuencia de PCE micronucleados en las hembras tratadas y una relación dosis respuesta positiva, cuando se evaluaron dosis de 500, 1000 y 2000 mg/kg por vía oral con el ensayo de micronúcleos en médula ósea de ratón(AU)

It was accomplished the study of the genotoxic effect of extract of Indigofera suffruticosa Mill. using the Salmonella/microsoma assay in strains TA 1535, TA 1537, TA 98 and TA 100 was positive in a plate incorporation protocol with concentrations ranging from 50 to 5000 mg/plate (¡À S9) for the strains TA 1535, TA 1537. The extract of Indigofera suffruticosa Mill. exhibited the significantly increment in the frequency of micronucleated polychromatic erythrocytes in female mice and dose-dependent genotoxicity to mouse bone marrow micronucleus test at the doses of 500, 1000 and 2000 mg/kg assayed(AU)

Genotoxicidad de Indigofera suffruticosa Mill / Genotocixity of Indigofera suffruticosa Mill

Se estudió el efecto genotóxico de un extracto de Indigofera suffruticosa Mill. mediante el ensayo Salmonella/microsomas con las líneas TA 1535, TA 1537, TA 98 y TA 100 que resultó positivo para el protocolo de incorporación en placas con las cepas TA 1535, TA 1537 con un rango de concentraciones de 50 a 5000 µg/placa (±S9). Mediante el ensayo de inducción de micronúcleos en médula ósea de ratón el extracto exhibió un aumento estadísticamente significativo en la frecuencia de PCE micronucleados en las hembras tratadas y una relación dosis respuesta positiva, cuando se evaluaron dosis de 500, 1000 y 2000 mg/kg por vía oral con el ensayo de micronúcleos en médula ósea de ratón.

It was accomplished the study of the genotoxic effect of extract of Indigofera suffruticosa Mill. using the Salmonella/microsoma assay in strains TA 1535, TA 1537, TA 98 and TA 100 was positive in a plate incorporation protocol with concentrations ranging from 50 to 5000 mg/plate (¡À S9) for the strains TA 1535, TA 1537. The extract of Indigofera suffruticosa Mill. exhibited the significantly increment in the frequency of micronucleated polychromatic erythrocytes in female mice and dose-dependent genotoxicity to mouse bone marrow micronucleus test at the doses of 500, 1000 and 2000 mg/kg assayed.

Evaluación genotóxica del extracto hidroalcohólico de Tamarindus indica L. empleando el ensayo de micronúcleos en médula ósea de ratón / Genotoxic assessment of hydroalcoholic extract of Tamarindus indica L using micronuclei assay in mouse bone marrow

El ensayo de micronúcleos en médula ósea de ratón, prueba incluida en la batería estándar de genotoxicidad, fue empleado para evaluar el potencial clastogénico y aneugénico de un extracto hidroalcohólico de Tamarindus indica L. Se utilizaron ratones NMRI de ambos sexos los que fueron administrados por vía intragástrica a razón de 10 mL/kg, separados 24 h, con sacrificio 24 h después de la última aplicación Se determinó el índice de genotoxicidad, porcentaje de eritrocitos policromáticos micronucleados en un total de 1 000 eritrocitos policromáticos por animal. Los índices de genotoxicidad de los grupos tratados con 500, 1000 y 2000 mg/kg de peso corporal del extracto, fueron estadísticamente significativos con respecto al grupo tratado con la sustancia control (H2O estéril). El extracto de Tamarindus indica L. resultó clastogénico, ya que produjo un aumento significativo en la frecuencia de micronúcleos de los eritrocitos policromáticos de la médula ósea y en la prueba de tendencia lineal de proporciones demostró una relación dosis-respuesta(AU)

Micronuclei assay in mouse bone marrow, test included in genotoxicity standard battery, was used to assess clastogenic and aneugenic potential of a hydroalcoholic extract of Tamarindus indica L. We used NMRI mice of both sexes, with administration by intragastric route at a rate of 10 mL/kg, in the space of 24 hours, sacrified 24 hours after last application. Genotoxicity rate, polychromatic micronucleated erythrocyte percentage in a total of 1 000 polychromatic erythrocytes per animal. Genotoxicity rates of treated groups using 500, 1000, and 2000 mg/kg extract/body weight were statistically significant as for group treated with control substance (H2O sterile). Extract of Tamarindus indica L was of clastogenic type, since give raise to a significant increase in micronuclei frequency of bone marrow polychromatic erythrocytes, and in ratios linear trend test showed a dosis-response relationship(AU)

Evaluación genotóxica del extracto hidroalcohólico de Tamarindus indica L. empleando el ensayo de micronúcleos en médula ósea de ratón / Genotoxic assessment of hydroalcoholic extract of Tamarindus indica L using micronuclei assay in mouse bone marrow

El ensayo de micronúcleos en médula ósea de ratón, prueba incluida en la batería estándar de genotoxicidad, fue empleado para evaluar el potencial clastogénico y aneugénico de un extracto hidroalcohólico de Tamarindus indica L. Se utilizaron ratones NMRI de ambos sexos los que fueron administrados por vía intragástrica a razón de 10 mL/kg, separados 24 h, con sacrificio 24 h después de la última aplicación Se determinó el índice de genotoxicidad, porcentaje de eritrocitos policromáticos micronucleados en un total de 1 000 eritrocitos policromáticos por animal. Los índices de genotoxicidad de los grupos tratados con 500, 1000 y 2000 mg/kg de peso corporal del extracto, fueron estadísticamente significativos con respecto al grupo tratado con la sustancia control (H2O estéril). El extracto de Tamarindus indica L. resultó clastogénico, ya que produjo un aumento significativo en la frecuencia de micronúcleos de los eritrocitos policromáticos de la médula ósea y en la prueba de tendencia lineal de proporciones demostró una relación dosis-respuesta.

Micronuclei assay in mouse bone marrow, test included in genotoxicity standard battery, was used to assess clastogenic and aneugenic potential of a hydroalcoholic extract of Tamarindus indica L. We used NMRI mice of both sexes, with administration by intragastric route at a rate of 10 mL/kg, in the space of 24 hours, sacrified 24 hours after last application. Genotoxicity rate, polychromatic micronucleated erythrocyte percentage in a total of 1 000 polychromatic erythrocytes per animal. Genotoxicity rates of treated groups using 500, 1000, and 2000 mg/kg extract/body weight were statistically significant as for group treated with control substance (H2O sterile). Extract of Tamarindus indica L was of clastogenic type, since give raise to a significant increase in micronuclei frequency of bone marrow polychromatic erythrocytes, and in ratios linear trend test showed a dosis-response relationship.

Evaluación del potencial genotóxico de Boerhavia erecta L / Evaluation of the genotoxic potential of Boerhavia erecta L

Se evaluó la actividad mutagénica de un extracto acuoso de follaje liofilizado de Boerhavia erecta L. Se emplearon 2 pruebas: de Ames e inducción de micronúcleos en médula ósea de ratón. En el ensayo de Ames, los resultados fueron negativos en todas las cepas probadas de Salmonella typhimurium: TA 1535, TA 1537, TA 98 y TA 100, con un protocolo de incorporación en placa y concentraciones hasta 5 mg de liofilizado/placa. En el ensayo de micronúcleos, se hicieron 2 administraciones orales a razón de 10 mL/kg, separadas 24 h, con sacrificio 24 h después de la última aplicación. Las dosis fueron 500, 1 000 y 2 000 mg de liofilizado/kg. No se observaron variaciones en la relación entre eritrocitos policromáticos y eritrocitos normocromáticos, indicador de toxicidad medular. Tampoco se encontraron alteraciones significativas en la frecuencia de eritrocitos policromáticos micronucleados entre los distintos grupos de tratamiento. Se comprobó que el extracto acuoso de follaje liofilizado de B erecta no parece inducir efectos mutagénicos en los 2 sistemas de ensayo donde se evaluó(AU)

Evaluación del potencial genotóxico de Boerhavia erecta L / Evaluation of the genotoxic potential of Boerhavia erecta L

Se evaluó la actividad mutagénica de un extracto acuoso de follaje liofilizado de Boerhavia erecta L. Se emplearon 2 pruebas: de Ames e inducción de micronúcleos en médula ósea de ratón. En el ensayo de Ames, los resultados fueron negativos en todas las cepas probadas de Salmonella typhimurium: TA 1535, TA 1537, TA 98 y TA 100, con un protocolo de incorporación en placa y concentraciones hasta 5 mg de liofilizado/placa. En el ensayo de micronúcleos, se hicieron 2 administraciones orales a razón de 10 mL/kg, separadas 24 h, con sacrificio 24 h después de la última aplicación. Las dosis fueron 500, 1 000 y 2 000 mg de liofilizado/kg. No se observaron variaciones en la relación entre eritrocitos policromáticos y eritrocitos normocromáticos, indicador de toxicidad medular. Tampoco se encontraron alteraciones significativas en la frecuencia de eritrocitos policromáticos micronucleados entre los distintos grupos de tratamiento. Se comprobó que el extracto acuoso de follaje liofilizado de B erecta no parece inducir efectos mutagénicos en los 2 sistemas de ensayo donde se evaluó

The mutagenic activity of an aqueous extract of freeze-dried foliage of Boerhavia erecta L. was evaluated. 2 tests were used: Ames' test and micronucleus induction in mouse bone marrow. In Ames' test, the results were negative in all the tested strains of Salmonella typhimurium : TA 1535, TA 1537, TA 98 and TA 100, with a protocol of incorporation to plaque and concentrations up to 5 mg of freeze-dried/plaque. In the micronucleus test, 2 oral doses of 10 mL/kg were administrated separated by 24 hours, with sacrifice 24 hours after the last application. The doses were 500, 1 000 and 2 000 mg of freeze-dried/kg. No variations were observed in the relation between polychromatic erythrocytes and normochromatic erythrocytes, an indicator of medullary toxicity. No significant alterations were observed in the frequency of the micronucleated polychromatic erythrocytes among the different treatment groups. It was proved that the aqueous extract of freeze-dried foliage of B. Erecta does not seem to induce mutagenic effects in the two assay systems where it was assessed.

Toxicidad de un extracto tánico de Pinus caribaea Morelet / Toxicity of a tanin extract from Pinus caribea Morelet

Se determinó la toxicidad aguda oral, dérmica y toxicogenética de un polvo de taninos obtenido a partir de un extracto acuoso de la corteza de Pinus caribaea Morelet secado por spray dry. En todos los casos se emplearon ratas Wistar de ambos sexos y peso corporal entre 150 y 200 g. Se empleó el ensayo de dosis límite y aplicación cutánea de parche oclusivo durante 24 h, para determinar la toxicidad aguda oral y dérmica, respectivamente. El polvo fue administrado en dosis de 2 000 mg/kg en ambas ocasiones. Después de 14 días de observación, los animales fueron sacrificados para realizarles autopsia y examen macroscópico de órganos y tejidos. El estudio toxicogenético se realizó en un modelo in vitro: el sistema Salmonella/microsoma (Ames) y otro in vivo: el ensayo de inducción de micronúcleos en médula ósea de ratón. En el ensayo de Ames se testaron las cepas TA 100, TA 98, TA 1535 y TA 1537 de Salmonella typhimurium con y sin activación metabólica en el rango de concentraciones de 50, 150, 500, 1 500 y 5 000 mg/placa. En el ensayo de inducción de micronúcleos se ensayaron dosis de 500, 1 000 y 2 000 mg/kg de peso corporal. Se comprobó que el polvo de taninos, obtenido a partir de un extracto acuoso de corteza de Pinus caribaea secado por spray dry, no es tóxico por administración oral y dérmica en los animales y es genotóxico in vitro e in vivo. Sería útil realizar otros estudios, con otras condiciones, para precisar la genotoxicidad de esta preparación(AU)

Toxicidad de un extracto tánico de Pinus caribaea Morelet / Toxicity of a tanin extract from Pinus caribea Morelet

Se determinó la toxicidad aguda oral, dérmica y toxicogenética de un polvo de taninos obtenido a partir de un extracto acuoso de la corteza de Pinus caribaea Morelet secado por spray dry. En todos los casos se emplearon ratas Wistar de ambos sexos y peso corporal entre 150 y 200 g. Se empleó el ensayo de dosis límite y aplicación cutánea de parche oclusivo durante 24 h, para determinar la toxicidad aguda oral y dérmica, respectivamente. El polvo fue administrado en dosis de 2 000 mg/kg en ambas ocasiones. Después de 14 días de observación, los animales fueron sacrificados para realizarles autopsia y examen macroscópico de órganos y tejidos. El estudio toxicogenético se realizó en un modelo in vitro: el sistema Salmonella/microsoma (Ames) y otro in vivo: el ensayo de inducción de micronúcleos en médula ósea de ratón. En el ensayo de Ames se testaron las cepas TA 100, TA 98, TA 1535 y TA 1537 de Salmonella typhimurium con y sin activación metabólica en el rango de concentraciones de 50, 150, 500, 1 500 y 5 000 mg/placa. En el ensayo de inducción de micronúcleos se ensayaron dosis de 500, 1 000 y 2 000 mg/kg de peso corporal. Se comprobó que el polvo de taninos, obtenido a partir de un extracto acuoso de corteza de Pinus caribaea secado por spray dry, no es tóxico por administración oral y dérmica en los animales y es genotóxico in vitro e in vivo. Sería útil realizar otros estudios, con otras condiciones, para precisar la genotoxicidad de esta preparación(AU)

Toxicidad de un extracto tánico de Pinus caribaea Morelet / Toxicity of a tanin extract from Pinus caribea Morelet

Se determinó la toxicidad aguda oral, dérmica y toxicogenética de un polvo de taninos obtenido a partir de un extracto acuoso de la corteza de Pinus caribaea Morelet secado por spray dry. En todos los casos se emplearon ratas Wistar de ambos sexos y peso corporal entre 150 y 200 g. Se empleó el ensayo de dosis límite y aplicación cutánea de parche oclusivo durante 24 h, para determinar la toxicidad aguda oral y dérmica, respectivamente. El polvo fue administrado en dosis de 2 000 mg/kg en ambas ocasiones. Después de 14 días de observación, los animales fueron sacrificados para realizarles autopsia y examen macroscópico de órganos y tejidos. El estudio toxicogenético se realizó en un modelo in vitro: el sistema Salmonella/microsoma (Ames) y otro in vivo: el ensayo de inducción de micronúcleos en médula ósea de ratón. En el ensayo de Ames se testaron las cepas TA 100, TA 98, TA 1535 y TA 1537 de Salmonella typhimurium con y sin activación metabólica en el rango de concentraciones de 50, 150, 500, 1 500 y 5 000 mg/placa. En el ensayo de inducción de micronúcleos se ensayaron dosis de 500, 1 000 y 2 000 mg/kg de peso corporal. Se comprobó que el polvo de taninos, obtenido a partir de un extracto acuoso de corteza de Pinus caribaea secado por spray dry, no es tóxico por administración oral y dérmica en los animales y es genotóxico in vitro e in vivo. Sería útil realizar otros estudios, con otras condiciones, para precisar la genotoxicidad de esta preparación

Acute oral, dermal and toxicogenetic toxicity of a spray dry-dried tanin powder from an aqueous extract of the wood of Pinus caribaea Morelet was determined. For all cases, Wistar rats of both sexes weighing 150-200g were used. Limit dose test and application of an occlusive patch on the skin for 24 hours determined the acute oral and dermal toxicities, respectively. The powder was administered at a dose of 2 000 mg/kg in both occasions. After 14 day-observation, the animals were killed to make autopsy and macroscopic test of organs and tissues. The toxicogenetic study was carried out in in vitro model called Salmonella/microsome system(Ames) and in vivo model, that is, the micronucleus induction test in the mouse bone marrow. In Ames test, strains TA 100, TA 98, TA 1535 and TA 1537 of Salmonella typhiumuriun with and without metabolic activation in the range of 50, 150, 500, 1 500 and 5 000 mg/plate concentrations were analyzed. Doses of 500, 1 000 and 2 000 mg/kg of body weight were tested in the micronuclei induction test. It was proved that the spray dry-dried tanin powder obtained from an aqueous extract of the wood of Pinus caribaea is not toxic by oral and dermal administration in the animals but it is genotoxic in vitro and in vivo. It will be advisable to perform other studies under different conditions so as to exactly determine the genotoxicity of this extract.

Passiflora incarnata L. y Senna alata (L) Roxo: Estudio toxicogenético que emplea 2 sistemas de ensayo a corto plazo / Passiflora incarnata L and Senna alata (L) Roxo: A toxicogenetic study using 2 short-term test systems

Con el objetivo de conocer el posible efecto toxicogenético de los extractos fluidos de Passiflora incarnata L. (pasiflora) y Senna alata (L.) Roxo (guacamaya francesa), se llevó a cabo un estudio mutagénico empleando 2 sistemas de ensayo a corto plazo, uno in vitro y otro in vivo: el modelo Aspergillus nidulans D-30 que detecta daño primario al ADN y el ensayo de inducción de micronúcleos en médula ósea de ratón el cual determina daño clastogénico y aneugénico. En el ensayo in vitro con el hongo Aspergillus nidulans D-30 (segregación mitótica) se evaluaron concentraciones del extracto fluido de Passiflora incarnata L.; desde 0,162 a 1,296 mg de sólidos totales/mL y para la Senna alata (L.) Roxo, concentraciones de 0,504 a 2,912 mg de sólidos totales/mL. En la prueba in vivo de inducción de micronúcleos se ensayaron para la Passiflora incarnata L. y para la Senna alata (L.) Roxo dosis de 0,607; 1,215; 2, 430 y 1 313,00; 2 625,00; 5 250,00 mg/kg de peso corporal (pc), respectivamente. En ambas baterías de ensayos genotóxicos ninguno de los 2 fitofármacos mostró daño celular ni actividad mutagénica(AU)