The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: Oxidative DNA damage, gluthatione depletion and stress proteins induction

Hassen, Wafa; Ayed-Boussema, Imen; Azqueta, Amaya; López, A.; Bacha, Hassen

doi:10.1016/j.tox.2007.01.015

Cited by 162 publications

(112 citation statements)

References 48 publications

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“…We have demonstrated that almost all ZEN toxic effects are prevented in vitro and in vivo using vitamin E (Abid-Essefi et al 2003;Ouanes et al 2003;El Golli et al 2006;Hassen et al 2007). Furthermore, a strong protection against ZEN-induced toxicity has been demonstrated to be conferred by extracts from cactus cladodes (Zourgui et al 2008;, radish (Raphanus sativus) (Ben Salah- Abbes et al 2009), or garlic (Allium sativum) (Abid-Essefi et al 2012).…”

Section: Introductionmentioning

confidence: 90%

“…For instance, ZEN has been demonstrated to be hepatotoxic (Maaroufi et al 1996;Obremski et al 1999;Conkova et al 2001;Bouaziz et al 2008), hematotoxic (Maaroufi et al 1996;Murata et al 2003;Abbes et al 2006a, b), nephrotoxic Abbes et al 2006a;Liang et al 2010), and toxic toward the intestinal tract (Abid-Essefi et al 2003). Different reports have shown in vitro and in vivo that ZEN induces cytotoxicity through reactive oxygen species (ROS) production leading to lipid peroxidation, DNA damages, and apoptosis by the mitochondrial pathway (Abid-Essefi et al 2004;Hassen et al 2007;Abbes et al 2007;Bouaziz et al 2008). ZEN was also shown to induce endoplasmic reticulum (ER) stress-mediated apoptosis in leukemic cells (Banjerdpongchai et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Salem

Prola

Boussabbeh

et al. 2015

Cell Stress and Chaperones

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Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. ZEN has been shown to be cytotoxic, genotoxic, and mutagenic in different cell types. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in ZENmediated toxicity in human intestine (HCT116) and kidney (HEK293) cells and evaluated the effects of the two common dietary compounds Quercetin (QUER) and Crocin (CRO). We show that ZEN treatment induces ER stress and activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP. 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 an activation of caspases and DNA damages. We also demonstrate that the antioxidant properties of QUER and CRO help to prevent ER stress and reduce ZEN-induced apoptosis in HCT116 and HEK293 cells. Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Salem

Prola

Boussabbeh

et al. 2015

Cell Stress and Chaperones

Self Cite

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“…However, the ZEA metabolites exhibited lower toxicity than ZEA, with zearalenol being the more active of the two metabolites [125]. In addition, oxidative damage is likely to be evoked as one of the main pathways of ZEA toxicity which may initiate event at least in part contribute to the mechanism of ZEA induced genotoxic and cytotoxic effects [126]. ZEA and its derivatives compete effectively with 17 -E2 for the specific binding sites of the oestrogen receptors (ERs) occurring in different organs.…”

Section: Trichothecenesmentioning

confidence: 99%

Mycotoxins-Induced Oxidative Stress and Disease

Omar¹

2013

Mycotoxin and Food Safety in Developing Countries

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“…Environmental or feed contaminants, such as ZEN (Hassen et al 2007) or DON (Kouadio et al 2005) which have the potential to induce oxidative stress and hypoxia in animal cells are plausible agents deregulating miRNA expression. Consequently, the aim of this study was to analyze the capability of the Fusarium toxins to affect expression of selected miRNAs in the liver and the colon of immature gilts during the 42 days of exposure to NOEL doses of ZEN, DON, and ZEN+DON mixture.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression profiles in liver and colon of sexually immature gilts after exposure to Fusarium mycotoxins

Brzuzan¹,

Woźny²,

Wolińska-Nizioł³

et al. 2015

Polish Journal of Veterinary Sciences

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To improve our knowledge of the role of microRNAs (miRs) in responses of the porcine digestive system to two Fusarium mycotoxins, zearalenone (ZEN) and deoxynivalenol (DON), we examined the expression of 7 miRs (miR-9, miR-15a, miR-21, miR-34a, miR-122, miR-125b, and miR-192), previously found to be deregulated in diseased liver and colon cells. In this study, immature gilts were exposed to NOEL doses of ZEN (40 μg/kg/d), DON (12 μg/kg/d), ZEN+DON (40+12 μg/kg/d), and placebo (negative control group) for 7, 14, 21, 28, 35, and 42 days. Before the treatment, expression levels of the selected miRs were measured in the liver, the duodenum, the jejunum, and the ascending and the descending colon of the gilts. Hierarchical clustering of the tissues by their miR expression profiles was consistent with what would be expected based on the anatomical locations and the physiological functions of the organs, suggesting that functions of the miRs are related to the specificities of the tissues in which they are expressed. A subset of 2 pairs of miRs (miR-21+miR-192 and miR-15a+miR-34a), which were assigned to two distinct clusters based on their tissue abundance, was then evaluated in the liver and the ascending and the descending colon during the treatment. The most meaningful results were obtained from the ascending colon, where a significant effect of the treatment was observed, suggesting that during the exposure to mycotoxins, the pathways involved in cell proliferation and survival were disordered. Changes in miR expression in the liver and the descending colon of the treated gilts were smaller, and were associated more with treatment duration than the exposure to ZEN, DON, or ZEN+DON. Further research should focus on identification of genes whose expression is regulated by these aberrantly expressed miRs. This should facilitate understanding of the miRNA-regulated biological effects of mycotoxins.

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The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: Oxidative DNA damage, gluthatione depletion and stress proteins induction

Cited by 162 publications

References 48 publications

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Mycotoxins-Induced Oxidative Stress and Disease

MicroRNA expression profiles in liver and colon of sexually immature gilts after exposure to Fusarium mycotoxins

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