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Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis

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Abstract

α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) are the major metabolites of Zearalenone (ZEN) and are known to induce many toxic effects. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in α- and β-ZOL-mediated toxicity in human kidney cells (HEK293) and evaluated the effect of a common dietary compound Crocin (CRO), from saffron. We show that α- and β-ZOL treatment induces ER stress as evidenced by the upregulation of the 78 kDa glucose-regulated protein (GRP78) and the Growth arrest and DNA damage-inducible protein (GADD34). Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm) and activation of caspases. We also demonstrate that the antioxidant properties of CRO help to prevent ER stress and reduce α- and β-ZOL-induced apoptosis in HEK293 cells. Our results suggest that saffron consumption might be helpful to prevent α- and β-ZOL-induced ER stress and toxicity.

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Abbreviations

ZEN:

Zearalenone

α-ZOL:

α-Zearalenol

β-ZOL:

β-Ζearalenol

CRO:

Crocin

ER:

endoplasmic reticulum

ΔΨm:

mitochondrial transmembrane potential

mtO2·- :

mitochondrial superoxide anion

UPR:

unfolded protein response

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Acknowledgments

This study was supported by “Le Ministère Tunisien de l’Enseignement Supérieur, de la Recherche Scientifique et de la Technologie” and by grants from LabEx LERMIT. A. Prola received a fellowship from GRRC. A. Guilbert received a fellowship from Region “Ile de France CORDDIM”.

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Authors and Affiliations

  1. Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia

    Intidhar Ben Salem, Manel Boussabbeh, Hassen Bacha & Salwa Abid-Essefi

  2. Faculty of Sciences of Bizerte, Carthage University, Tunis, Tunisia

    Intidhar Ben Salem & Manel Boussabbeh

  3. INSERM UMR-S 769, LabEx LERMIT, Châtenay-Malabry, France

    Alexandre Prola, Arnaud Guilbert & Christophe Lemaire

  4. Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France

    Christophe Lemaire

  5. Université de Versailles Saint Quentin en Yvelines, Versailles, France

    Christophe Lemaire

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  1. Intidhar Ben Salem
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  2. Manel Boussabbeh
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  3. Alexandre Prola
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  4. Arnaud Guilbert
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  5. Hassen Bacha
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  6. Christophe Lemaire
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  7. Salwa Abid-Essefi
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Correspondence to Salwa Abid-Essefi.

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Responsible editor: Philippe Garrigues

Highlights

α-Zearalenone and β-Zearalenol trigger ER stress in HEK293 cells

α-Zearalenone and β-Zearalenol induce apoptosis via activation of the mitochondrial pathway

CRO protect cells against α/β-Zearalenol-induced ER stress and apoptosis

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Ben Salem, I., Boussabbeh, M., Prola, A. et al. Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis. Environ Sci Pollut Res 23, 15504–15514 (2016). https://doi.org/10.1007/s11356-016-6741-y

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