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2011, Número 4

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Vet Mex 2011; 42 (4)


Genotoxicidad de la furazolidona y la forma libre de su metabolito 3-amino-2-oxazolidona, mediante la prueba de micronúcleos en linfocitos humanos

Barragán HEÁ, Herrera MLA, Ocampo CL, Sumano LH

Idioma: Español/Inglés
Referencias bibliográficas: 54
Paginas: 289-298
Archivo PDF: 204.93 Kb.


RESUMEN

El objetivo de este estudio fue evaluar los efectos genotóxicos del metabolito principal de la furazolidona 3-amino-2-oxazolidona (AOZ) que usualmente se encuentra unido a la proteína (AOZ-UP). Debido a que no se dispone para investigación biomédica de AOZ-UP, se utilizó la forma libre de AOZ (AOZ-L) como desafío genotóxico por medio de la técnica de cuantificación de micronúcleos inducidos en linfocitos humanos. El nivel de exposición de linfocitos a AOZ-libre fue establecido con base en la determinación por cromatografía líquida de alta resolución (CLAR) de los residuos de AOZ-UP encontrados en músculo e hígado de pollos, producidos en forma comercial, expuestos a furazolidona (FZD) por medio del alimento a dosis de 0.11% y 0.22%, permitiendo un tiempo de retiro de 7 días. Se conformaron dos grupos furazolidona (FZD) con las siguientes concentraciones de 10 µM (225 mg/g), 1 µM (225 mg/g), 0.1 µM (22.5 mg/g), y 0.001 µM (0.225 mg/g), así como el grupo testigo negativo sulfoxido de dimetilo (DMSO) 10-3 µM (0.130 mg/g) y el testigo positivo arsénico 10-3 µM (0.747 mg/g). quantitaPara AOZ-libre las concentraciones fueron 0.01 µM (1.020 mg/g); 0.001 µM (0.102 mg/g); 0.0005 µM (0.051 mg/g); y 0.0001 µM (0.001 mg/g) con los mismos grupos testigo. Los resultados muestran que la furazolidona a concentraciones de 1.0 µM y 0.1 µM posee un efecto genotóxico bien definido. El grado de asociación se calculó por medio del riesgo relativo y prueba de ANDEVA, que mostró el efecto estadísticamente significativo al compararlo con el grupo testigo negativo (P = 0.001; P = 0.03 y P = 0.04, respectivamente). Para AOZ-L las mismas pruebas estadísticas mostraron que sólo la concentración 0.01 µM era capaz de inducir un efecto genotóxico. Estos resultados sugieren que la furazolidona como sal pura es potencialmente capaz de inducir efectos genotóxicos en humanos, en los que no se apoya su uso. En contraste, sólo la concentración más alta de AOZ-L mostró un efecto similar, pero dicha concentración es mayor que la encontrada como residual a los siete días de retiro y puede considerársele como un peligro mucho menor para la salud pública que el compuesto progenitor. Dada la falta de evidencia científica del efecto genotóxico del AOZ-UP no se pueden realizar comparaciones adicionales con lo obtenido aquí para AOZ-L, pero parecería poco probable calificar a los residuos de AOZ-UP como peligros reales para la salud pública, por lo que se requieren pruebas adicionales.


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