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

alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-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 alpha- and beta-ZOL-mediated toxicity in human kidney cells (HEK293) and evaluated the effect of a common dietary compound Crocin (CRO), from saffron. We show that alpha- and beta-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 (Delta Psi m) and activation of caspases. We also demonstrate that the antioxidant properties of CRO help to prevent ER stress and reduce alpha- and beta-ZOL-induced apoptosis in HEK293 cells. Our results suggest that saffron consumption might be helpful to prevent alpha- and beta-ZOL-induced ER stress and toxicity.