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Ben Salem I.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Ben Salem I.,University of Carthage | Prola A.,French Institute of Health and Medical Research | Boussabbeh M.,Laboratory for Research on Biologically Compatible Compounds LRSBC | And 7 more authors.
Cell Stress and Chaperones | Year: 2015

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 ZEN-mediated 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. © 2015, Cell Stress Society International. Source


Ben Salem I.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Ben Salem I.,University of Carthage | Boussabbeh M.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Boussabbeh M.,University of Carthage | And 7 more authors.
Environmental Science and Pollution Research | Year: 2016

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. © 2016 Springer-Verlag Berlin Heidelberg Source


Zouaoui N.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Zouaoui N.,University of Carthage | Mallebrera B.,University of Valencia | Berrada H.,University of Valencia | And 3 more authors.
Food and Chemical Toxicology | Year: 2016

Mycotoxins are produced by different genera of fungi; mainly Aspergillus, Penicillium and Fusarium. The natural co-occurrence of beauvericin (BEA), patulin (PAT) and sterigmatocystin (STE) has been proved in feed and food commodities. This study investigates the cytotoxicity of individual and combined mycotoxins BEA, PAT and STE. The cytotoxicity on immortalized ovarian cells (CHO-K1) was evaluated using the MTT assay. After 24, 48 and 72 h, the IC50 values were 2.9 μM for PAT and ranged from 10.7 to 2.2 μM and from 25.0 to 12.5 μM for BEA and STE, respectively. Cytotoxic interactions were assayed by the isobologram method, which provides a combination index (CI) value as a quantitative measure of the three mycotoxin interaction's degree. Binary and tertiary combinations showed a dose dependent effect. At low fraction affected, mycotoxin combinations were synergetic; whereas, at higher fraction affected, the combinations showed additive effect. Our results indicate that the co-occurrence of low concentrations of mycotoxin in food may increase their toxic effects. © 2016 Elsevier Ltd. Source


Zaied C.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Abid S.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Mtiraoui N.,Research Unit of Haematological and Autoimmune Diseases | Zellema D.,CHU | And 2 more authors.
Genetic Testing and Molecular Biomarkers | Year: 2012

Aim: Human cytochrome P450 3A and glutathione S-transferase (GST) enzymes evolved to catalyze the metabolism of numerous common therapy drugs and endogenous molecules. Members of the CYP3A are the majority expressed in human liver and intestine. The genetic factors play an important role in the interindividual variability in CYP3A and GST activity. Detection of CYP3A4 and GST variant alleles and knowledge about their allelic frequency in specific ethnic groups are important to lead to individualized drug dosing and improved therapeutics. Methods: We determined the allelic frequency of the CYP3A4*18 and GSTP1 in a group of 138 healthy Tunisian subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. It is based on a specific PCR product cut by restriction endonucleases. This method offers the advantage of cutting DNA by the appropriate restriction enzyme at the correct mutation site hence enhancing its reliability. Electrophoretic separation demonstrates the presence (or absence) of restriction sites. Results: In the group of 138 unrelated individuals, the frequencies of the CYP3A4*18 and GSTP1 variant allele in this Tunisian population were 0.02 and 0.01, respectively. Conclusions: The present study describes polymorphisms of Cyp3A4 and GST among Tunisian subjects. We developed a simple assay for the detection of the CYP3A4*18 and GSTP1 polymorphisms and we compared our allelic frequencies to other populations. No significant difference was obtained. This study provides the first analysis of CYP3A4*18 and GSTP1 mutant allele frequencies in the Tunisian population. © Copyright 2012, Mary Ann Liebert, Inc. Source


Zaied C.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Zouaoui N.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Bacha H.,Laboratory for Research on Biologically Compatible Compounds LRSBC | Abid S.,Laboratory for Research on Biologically Compatible Compounds LRSBC
Food Control | Year: 2012

Fusarium mycotoxins are worldwide occurring in cereals and they are frequently reported in fresh or stored grains. Cereals represent a staple food for the Tunisian population; it therefore has a high social, economic and nutritional relevance. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by a variety of Fusarium fungi in temperate and warm countries. Fungi-producing ZEN contaminates corn, barley, wheat, sorghum and rice. A total of 205 samples of wheat were collected during the harvest year of 2010 from the major cropping areas in Tunisia and they were analyzed for zearalenone contamination. The aim of this study was to investigate for the first time the presence of ZEN in widely-consumed cereals in Tunisia, especially durum and tender wheat, to compare the levels of contamination by ZEN with the European norms and to suggest some factors that can promote the production of ZEN in Tunisia. To perform this study, we developed and validated in our laboratory conditions an HPLC method for quantitative analysis of ZEN in solid cereal samples. Our results showed that the incidence of ZEN contamination was 75%. The levels of contamination determined in the positive samples ranged between 3 and 560 μg/kg with a mean value of 60 μg/kg. These important amounts of ZEN in wheat can be attributed to the Tunisian climate, warm temperature and prolonged wetness witch are favor to Fusarium growth and mycotoxin production during the cultivation and the final ripening period of wheat grains. © 2011 Elsevier Ltd. Source

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