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Efectos tóxicos de la zearalenona y sus metabolitos en líneas celulares

Authors: Tatay Dualde, Elena;

Efectos tóxicos de la zearalenona y sus metabolitos en líneas celulares

Abstract

La zearalenona (ZEA) y sus metabolitos α-zearalenol (α-ZOL) y β-zearalenol (β-ZOL), son metabolitos secundarios de hongos del genero Fusarium. La ZEA se absorbe y se metaboliza a α-ZOL y β-ZOL. Tanto la ZEA como sus metabolitos producen sus efectos tóxicos por la interacción con los receptores endocrinos aunque no es el único mecanismo por el cual pueden producir toxicidad. Se sabe que, además de disruptores endocrinos la ZEA y sus metabolitos son inmunotóxicos, hepatotóxicos y hematotóxicos causando alteraciones en el sistema reproductivo. La citotoxicidad de la ZEA y sus metabolitos ha sido determinada por distintos tiempos de exposición en diferentes células de mamíferos obteniéndose diferentes valores de IC50. Se investigó la conversión de ZEA y sus metabolitos en estos u otros derivados de ZEA por células CHO-K1 y HepG2 observando diferentes derivados de la ZEA y sus metabolitos. La exposición a estas micotoxinas causa estrés oxidativo observándose un aumento de las especies reactivas de oxigeno (ROS) que es proporcional al tiempo de exposición y la concentración de las micotoxinas. Se ha visto que este aumento de ROS conduce a una alteración de las vías metabólicas, disminución de los antioxidantes celulares y provoca que se oxiden estructuras macromoleculares, entre las que se encuentran las proteínas y lípidos de las membranas celulares y el ADN. Se evaluó la actividad estrogénica de la ZEA y sus metabolitos usando células de cáncer de mama humano (MCF-7) y se observó un aumento de esta actividad siendo el α-ZOL el que producía un mayor aumento de la actividad estrogénica. Se determinó si la ZEA y sus metabolitos activan los mecanismos de defensas antioxidantes en las células CHO-K1 y HepG2. Para ello, se determinó la actividad del glutatión (GSH) y de las enzimas catalasa (CAT), superóxido dismutasa (SOD) y glutatión peroxidasa (GPx) tras exponer las células durante 24 h en las células CHO-K1 y HepG2. Los resultados mostraron una disminución de los niveles de GSH y de la actividad de la catalasa. Mientras que se evidenció un aumento en la actividad de la SOD y GPx. Todos estos efectos tóxicos pueden conducir a un riesgo en la salud humana.

Zearalenone (ZEA) and its metabolites α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) are secondary metabolites of Fusarium fungy. ZEA is absorbed and metabolized to α-ZOL and β-ZOL. Boths ZEA and its metabolites produce their toxic effects through interactions with endocrine receptors, although it is not the only mechanism by which they can produce toxicity. It is known that in addition to endocrine disruptors ZEA and its metabolites are immunotoxic, hepatotoxic and hematotoxic causing alterations in the reproductive system. The cytotoxicity of ZEA and its metabolites has been determined by different exposure times in different mammalian cells obtaining different IC50 values. It was investigated the conversion of ZEA and its metabolites into these or other ZEA derivatives in CHO-K1 and HepG2 cells by observing different derivates of ZEA and its metabolites. The exposure to these mycotoxins causes oxidative stress observing an increase of the reactive oxygen species (ROS) that is proportional to the time of exposure and the concentration of the mycotoxins. It is seen that this growth of ROS leads to an alteration of metabolic pathways, a decrease in cellular antioxidants and causes oxidation of macromolecular structures, among which are the proteins and lipids of cell membranes and DNA. The estrogenic activity of ZEA and its metabolites was evaluated using human breast cancer cells (MCF-7) and an increase of this activity was observed. α-ZOL was the one that produced a greater increase of the estrogenic activity. It was determined if ZEA and its metabolites activate the mechanisms of antioxidant defenses in CHO-K1 and HepG2 cells. For this purpose, the activity of glutathione (GSH) and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined after exposed the cells for 24 h in CHO-K1 and HepG2 cells. The results showed a decrease in GSH levels and a decrease in catalase activity. While an increase in the activity of SOD and GPx was evidenced. All these toxic effects can lead to a risk to human health.

Keywords

HepG2, zearalenona, CHO-K1, citotoxicidad

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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