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Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are important food-borne mycotoxins that have been implicated in human health. In this study, independent and combinative toxicities of AFB1 and OTA were tested in cultured monkey kidney Vero cells. The experiments reported here were conducted to evaluate the effect of these toxins on cell viability followed by the determination of cell death pathways, using the quantification of DNA fragmentation and the expression of p53 and bcl-2 protein levels. Our results showed that AFB1 and OTA caused a marked decrease of cell viability in a dose-dependent manner. Under the same conditions, these mycotoxins increased fragmented DNA levels. In addition, p53 was activated in response to DNA damage and the expression of the antiapoptotic factor bcl-2 decreased significantly. According to these data, AFB1 and OTA seemed to be involved in an apoptotic process. Moreover, combined AFB1 and OTA induced all the toxicities observed with the mycotoxins separately. Therefore, this combination was classified as an additive response of the two mycotoxins.

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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Diazinon (DZ) (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl]phosphorothioate) is an organophosphate pesticide which is extensively used to control household insects and fruit and vegetable crops. The exposure to this pesticide has been linked to the development of the serious problem in several experimental animals. The contamination of food by DZ may increase its danger to humans. The aim of this study was to investigate the toxic effect of DZ on intestine using an in vitro model (HCT116). Therefore, we evaluated the cell viability, elucidated the generation of free radicals, measured the mitochondrial membrane potential, and valued DNA fragmentation. Our results showed that DZ is cytotoxic to HCT116. It causes oxidative damage through the generation of free radicals and induces lipid peroxidation and DNA fragmentation. We also demonstrated that such effects can be responsible for DZ-induced apoptosis.

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