Protección de la Spirulina maxima sobre la citotoxicidad de la hidroxiurea en células embrionarias de ratón / Protection of Spirulina maxima on cytotoxicity of hydroxyurea in mouse embryonic cells / Proteção de Spirulina maxima em citotoxicidade de hidroxiureia em células embrionárias de camundongo

La Spirulina maxima (SP) tiene efectos farmacológicos protectores por su contenido de ficobiliproteínas que están relacionados con su actividad antioxidante. La hidroxiurea (HU) es un fármaco antineoplásico, citotóxico y teratógeno que implica la inducción del estrés oxidativo. El objetivo de este trabajo fue determinar si la SP y su extracto acuoso de proteína (SPE) protegen contra el efecto citotóxico de HU en cultivos celulares primarios a partir de embriones de ratón de once días. Los efectos de SP, SPE e HU sobre la viabilidad celular se determinaron por el ensayo de fluorescencia de resazurina en cultivos celulares de embriones completos de ratones de once días, de encéfalo y de brotes de extremidades anteriores. Se demostró que ni SP ni su extracto provocaron efectos citotóxicos en ninguna concentración ensayada, por lo que se aumentaba la viabilidad celular. Se encontró que las células expuestas a HU de embriones completos y encéfalo mostraron mayor toxicidad que las células de los miembros anteriores. La SP y el SPE protegieron contra la citotoxicidad de HU de una manera dependiente de la concentración hasta 48 h después de la exposición al fármaco. Este efecto podría ser adecuado para prevenir la muerte celular que deriva en un proceso teratogénico, atribuido a sus propiedades antioxidantes.

Spirulina maxima (SP) has protective pharmacological effects that are related to the antioxidant activity due to its phycobiliprotein content. Hydroxyurea (HU) is an antineoplastic, cytotoxic and teratogenic drug, which involves the induction of oxidative stress. The aim of this study was to determine whether SP and its aqueous protein extract (SPE) protect against the cytotoxic effect of HU in primary cell cultures from mouse embryos. The effects of SP, SPE, and HU on cell viability were determined by resazurin fluorescence assay in whole embryo cell cultures, encephalon, and eleven-day-old forehead bud outbreaks. It was shown that neither SP nor its extract caused cytotoxic effects at any concentration tested, increasing cell viability. It was found that cells exposed to HU of whole embryos and encephalon showed higher toxicity than cells of the previous limbs. SP and SPE protected HU cytotoxicity in a concentration-dependent manner up to 48 hours after exposure to the drug. This effect could be adequate to prevent cell death resulting in a teratogenic process attributed to its antioxidant properties.

Spirulina maxima (SP) tem efeitos farmacológicos protetores devido a seu conteúdo de ficobiliproteínas, que estão relacionadas com sua atividade antioxidante. A hidroxiureia (HU) é uma droga antineoplásica, citotóxica e teratogênica, que envolve a indução do estresse oxidativo. O objetivo deste estudo foi determinar se a SP e seu extrato aquoso de proteína (SPE) protegem contra o efeito citotóxico da HU em culturas celulares primárias a partir de embriões de camundongo de onze dias. Os efeitos de SP, SPE e HU na viabilidade celular foram determinados pelo ensaio de fluorescência de resazurina em culturas celulares de embriões inteiros de camundongos de onze dias, de encéfalo e de surtos de extremidades anteriores. Demonstrou-se que nem a SP nem seu extrato causaram efeitos citotóxicos em qualquer concentração testada, aumentando a viabilidade celular. Verificou-se que as células expostas à HU de embriões completos e encéfalo mostraram maior toxicidade do que as células dos membros anteriores. SP e SPE protegem contra a citotoxicidade de HU de forma dependente da concentração até 48 h após a exposição ao medicamento. Esse efeito poderia ser adequado para prevenir a morte celular, que resulta em um processo teratogênico atribuído a suas propriedades antioxidantes.

Effect of Spirulina maxima and its protein extract on micronuclei induction by hydroxyurea in pregnant mice and their fetuses.

The purpose of the present report was to determine the inhibitory effect of Spirulina maxima (Sm) and its protein extract (PE), mainly consisting of C-phycocyanin, on the increase in micronuclei and bone marrow cytotoxicity induced by hydroxyurea (HU) in pregnant mice and their fetuses. The two tested antimutagenic agents were administered daily from day 10 to day 18 of pregnancy, and HU (300 mg/kg) was administered once on day 16 of the assay. The experimental design also included mice that were administered only Sm or PE (1000 and 400 mg/kg, respectively), two control groups that were administered with vehicles (water and 0.5% Tween 80), and one additional group that was treated solely with HU. Blood samples from the pregnant mice and their fetuses were examined at day 19 of pregnancy. Significant increases in the number of micronucleated polychromatic erythrocytes and in the total number of micronucleated erythrocytes were observed in all HU-treated animals. In contrast, similarly low numbers of micronuclei were observed in the two control groups and in the groups treated with Sm and PE alone. The administration of Sm (100, 500, and 1000 mg/kg) and PE (100, 200, and 400 mg/kg) to HU-treated animals conferred moderate genotoxic protection (∼30%) and some protection against the cytotoxicity induced by HU in mice. The obtained results provide new information regarding the capacity of the tested agents to confer protection to adult mice and transplacentally, as well as on a specific subclass of micronuclei.

Spirulina maxima and its protein extract protect against hydroxyurea-teratogenic insult in mice.

Congenital malformations are one of the major causes of child mortality all over the world. In order to prevent them it is necessary to find substances that act as anti-teratogenic agents. In this study hydroxyurea (HU), an antineoplastic and teratogenic drug, was administered to pregnant mice because one of its major mechanisms of teratogenesis is the production of reactive oxygen species (ROS). The aim of this work was to determine if Spirulina maxima (SP) and its aqueous protein extract could protect against HU-teratogenic insult in mouse embryos. SP has been used for a long time because of its nutritional and pharmacological properties. The antioxidant activity, one of the most important, is related to the protein extract due to its content of phycobiliproteins. It was observed that neither SP nor its extract provoked teratogenic effects at any dose tested and even increased vitelline yolk sac circulation. Dams exposed to HU (30 mg/kg, i.p.) presented embryos with multiple alterations in their development. Groups treated with SP or its extract, before and after HU exposure, showed a protector effect in a dose-dependent manner. TBARS test confirmed that the protection effect was related to the antioxidant activity of both SP and its extract.