{"id":115679,"date":"2018-03-11T10:44:21","date_gmt":"2018-03-11T10:44:21","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/disminucion-de-los-efectos-genotoxicos-citotoxicos-y-radiosensibilizante-de-bisfosfonatos-mediante-antioxidantes-un-modelo-experimental\/"},"modified":"2018-03-11T10:44:21","modified_gmt":"2018-03-11T10:44:21","slug":"disminucion-de-los-efectos-genotoxicos-citotoxicos-y-radiosensibilizante-de-bisfosfonatos-mediante-antioxidantes-un-modelo-experimental","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/toxicologia\/disminucion-de-los-efectos-genotoxicos-citotoxicos-y-radiosensibilizante-de-bisfosfonatos-mediante-antioxidantes-un-modelo-experimental\/","title":{"rendered":"Disminuci\u00f3n de los efectos genot\u00f3xicos, citot\u00f3xicos y radiosensibilizante de bisfosfonatos mediante antioxidantes: un modelo experimental"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Amparo Olivares Rueda <\/strong><\/h2>\n<p>Resumen objetivos: los objetivos esta tesis doctoral son determinar los efectos genot\u00f3xicos y citot\u00f3xicos de los bisfosfonatos en combinaci\u00f3n con la radiaci\u00f3n ionizante, con el fin de evaluar un posible efecto t\u00f3xico sin\u00e9rgico de ambos tratamientos y determinar un posible efecto protector de algunos antioxidantes que podr\u00eda permitir un aumento del efecto terap\u00e9utico y\/o de las dosis administradas. metodolog\u00eda: el efecto genot\u00f3xico se estudi\u00f3 con el test de micron\u00facleos en linfocitos humanos bloqueados citocin\u00e9ticamente antes y despu\u00e9s de una irradiaci\u00f3n de 2 gy;  mientras que el efecto citot\u00f3xico se estudi\u00f3 con un ensayo de viabilidad celular (mtt) en las l\u00edneas celulares normales de pr\u00f3stata pnt2,  tumorales de pr\u00f3stasta tramp-c1 y de melanoma metast\u00e1sico b16f10 antes y despu\u00e9s de la exposici\u00f3n a diferentes dosis de rayos x (0-20 gy) en tratamientos combinados con bisfosfonatos (\u00e1cido zoledr\u00f3nico, ibandronato y pamidronato) y con antioxidantes (apigenina, carnosol y \u00e1cido rosmar\u00ednico). resultados y conclusiones: los bisfosfonatos presentaron un efecto citot\u00f3xico seg\u00fan la dosis administrada, destacando la capacidad genot\u00f3xica y citot\u00f3xica de \u00e1cido zoledronico; y un efecto citot\u00f3xico sin\u00e9rgico en el tratamiento combinado de radiaci\u00f3n ionizante con \u00e1cido zoledronico. La administraci\u00f3n de ciertos antioxidantes junto con los bisfosfonatos reduce la toxicidad de estos. La administraci\u00f3n de antioxidantes disminuye el efecto lesivo inducido por la radiaci\u00f3n ionizante, comport\u00e1ndose como una sustancia radioprotectora tanto del tumor como de las c\u00e9lulas normales no tumorales. Sin embargo, el carnosol y el \u00e1cido rosmar\u00ednico mostraron un efecto parad\u00f3jico en las c\u00e9lulas del melanoma, ya que se comportan como radiosensibilizadores en estas c\u00e9lulas, por lo que podr\u00edan permitir una nueva estrategia que implicar\u00eda un efecto radiosensibilizador en estas c\u00e9lulas tumorales, pero al mismo tiempo con un efecto radioprotector en el tejido normal adyacente incluido en el mismo campo de irradiaci\u00f3n.   abstract objectives: the aims this doctoral thesis are determine the genotoxic and cytotoxic effects of bisphosphonates both separately and in combination with ionizing radiation, in order to assess the possible existence of a synergically toxic effect resultant from both therapies and determine the potentially protective effect of antioxidants against the toxicity induced by the bisphosphonates which might enable an increase in their therapeutic effect and\/or the dose administered.  methods: the genotoxic effect was studied by means of the micronucleus test in cytokinesisblocked cells of human lymphocytes irradiated before and after a 2 gy irradiation, while the cytotoxic effect was studied by a cell viability test (mtt) in the pnt2, tramp-c1 and b16f10 cell line before and after exposure to different x-ray doses (0-20 gy) in the combined treatments with bisphosphonates (zoledronic acid, ibandronate and pamidronate) and antioxidants (apigenin, carnosol and rosmarinic acid). results &amp; conclusions: the bisphosphonates tested present a dose-dependent cytotoxic effect, highlighting the genotoxic and cytotoxic capacity of zoledronic acid and a synergic cytotoxic effect exists in the combined treatment of ionizing radiation plus zoledronic acid, while the administration of certain antioxidants together with bisphosphonates reduces toxicity. The administration of certain antioxidants diminishes the toxic effects induced by the ionizing radiation, behaving in a radioprotective manner in both tumour and normal, non-tumour cells. However, carnosol and rosmarinic acid display a paradoxical effect in melanoma cells since they behave in a radiosensitizing manner in melanoma cells only and thus might allow for a new strategy involving a radiosensitizing effect in the aforementioned cells, yet at the same time a protective effect in normal adjacent tissue.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Disminuci\u00f3n de los efectos genot\u00f3xicos, citot\u00f3xicos y radiosensibilizante de bisfosfonatos mediante antioxidantes: un modelo experimental<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Disminuci\u00f3n de los efectos genot\u00f3xicos, citot\u00f3xicos y radiosensibilizante de bisfosfonatos mediante antioxidantes: un modelo experimental <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Amparo Olivares Rueda <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/05\/2014<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Miguel Alcaraz Ba\u00f1os<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco Solano mu\u00f1oz <\/li>\n<li>m. josefa Y\u00e1\u00f1ez gascon (vocal)<\/li>\n<li>cristina Martinez conesa (vocal)<\/li>\n<li>Jos\u00e9 Luis Navarro fern\u00e1ndez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Amparo Olivares Rueda Resumen objetivos: los objetivos esta tesis doctoral son determinar los efectos genot\u00f3xicos y citot\u00f3xicos [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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