RESUMEN
Lungs require an adequate supply of vitamin A for normal embryonic development, postnatal maturation, and maintenance and repair during adult life. However, recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer, although the mechanisms underlying this effect are still unknown. Here, the authors studied the effect of vitamin A supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A supplementation either at therapeutic (1000 and 2500 IU/kg) or excessive (4500 and 9000 IU/kg) doses for 28 days induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (EC 1.11.1.6; CAT) and superoxide dismutase (EC 1.15.1.1, SOD) activities and immunocontents. These results altogether suggest that vitamin A supplementation causes significant changes in redox balance the free radical status in lungs, which are frequently associated to severe lung dysfunction.
Asunto(s)
Catalasa/metabolismo , Suplementos Dietéticos , Pulmón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Vitamina A/farmacología , Animales , Suplementos Dietéticos/toxicidad , Relación Dosis-Respuesta a Droga , Immunoblotting , Peroxidación de Lípido/efectos de los fármacos , Pulmón/enzimología , Masculino , Oxidación-Reducción , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Vitamina A/toxicidadRESUMEN
Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.