RESUMEN
Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.
Asunto(s)
Daño del ADN , Ditiocarba/toxicidad , Maneb/toxicidad , Zineb/toxicidad , Animales , Recuento de Eritrocitos , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Masculino , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Pruebas de Micronúcleos , Ratas WistarRESUMEN
Dithiocarbamates are nitrogen- and sulfur-containing compounds commonly used in pharmacology, medicine and agriculture. The molecular effects of dithiocarbamates on neuronal cell systems are not fully understood, especially in terms of their ability to accumulate copper ions inside the cell. In this work, the molecular effects of N,N-diethyldithiocarbamate (DEDTC) were studied in human SH-SY5Y neuroblastoma cells to determine the role of copper in the DEDTC toxicity and the pathway trigged in cell by the complex Cu-DEDTC. From concentration-dependent studies, we found that 5 µM of this compound induced a drastic decrease in viable cells with a concomitant accumulation in intracellular copper resulted from complexation with DEDTC, measured by atomic absorption spectroscopy. The mechanism of DEDTC-induced apoptosis in neuronal model cells is thought to occur through the death receptor signaling triggered by DEDTC-copper complex in low concentration that is associated with the activation of caspase 8. Our results indicated that the mechanism of cell death involves cytochrome c release forming the apoptosome together with Apaf-1 and caspase 9, converting the caspase 9 into its active form, allowing it to activate caspase 3 as observed by immunofluorescence. This pathway is induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions present in the culture medium and transports them into the cell, suggesting that the DEDTC by itself was not able to cause cell death and the major effect is from its copper-complex in neuroblastoma cells. The present study suggests a role for the influence of copper by low concentrations of DEDTC in the extracellular media, the absorption and accumulation of copper in the cell and apoptotic events, induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions.
Asunto(s)
Caspasas/metabolismo , Cobre/metabolismo , Citocromos c/metabolismo , Ditiocarba/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Humanos , Neuroblastoma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
El ditiocarbamato 43GV040 presenta manifestaciones neurotóxicas cuando se administra en dosis letales a ratones, ratas y perros, por lo que se propuso hallar una evaluación biológica que indicara el comportamiento de esta toxicidad, así como disponer de una evaluación que corroborara la integridad del producto durante sus estudios preclínicos. En este estudio se demostró que existe una correspondencia entre las determinaciones biológicas y químicas propuestas; pudiéndose anunciar que tanto la materia prima como las formas farmacéuticas, se encuentran aptas en sus parámetros de calidad, cuando realizado el ensayo bajo las condiciones expuestas, el grado de neurotoxicidad se encuentra entre 40 y 50 transcurridos 45 min de la administración del producto. Se presentan datos sobre la estabilidad del producto almacenado en diferentes condiciones hasta el año de elaborado(AU)