In vitro mechanisms of Beauvericin toxicity: A review.

Beauvericin (BEA) is a mycotoxin produced by many species of fungus Fusarium and by Beauveria bassiana; BEA is a natural contaminant of cereals and cereals based products and possesses a wide variety of biological properties. The mechanism of action seems to be related to its ionophoric activity, that increases ion permeability in biological membranes. As a consequence, BEA causes cytotoxicity in several cell lines and is capable to produce oxidative stress at molecular level. Moreover, BEA is genotoxic (produces DNA fragmentation, chromosomal aberrations and micronucleus) and causes apoptosis with the involvement of mitochondrial pathway. However, several antioxidant mechanisms protect cel…

In silico and in vitro prediction of the toxicological effects of individual and combined mycotoxins.

3-Acetyldeoxynivalenol (3-AcDON) and 15-acetyldeoxynivalenol (15-AcDON) are converted to deoxynivalenol (DON) in vivo and their simultaneous presence may increase DON intake. Mixtures of DON and its derivatives are a public health concern. In this study DON, 3-AcDON and 15-AcDON were evaluated in vitro and in silico. The in vitro cytotoxicity of DON and its derivatives individually and combined was determined by the Neutral Red (NR) assay in human hepatocarcinoma (HepG2) cells. The concentrations tested were from 1.25 to 15 μM (DON) and from 0.937 to 7.5 μM (DON derivatives). The IC50 values were from >15 to 2.55 μM (DON), from 1.77 to 1.02 μM (3-AcDON), and from 4.05 to 1.68 μM (15-AcDON).…

Beauvericin-induced cytotoxicity via ROS production and mitochondrial damage in Caco-2 cells.

The cytotoxicity of beauvericin (BEA) on human colon adenocarcinoma (Caco-2) cells was studied as a function of time. Moreover, the oxidative damage and cell death endpoints were monitored after 24, 48 and 72 h. After BEA exposure, the IC₅₀ values ranged from 1.9 ± 0.7 to 20.6 ± 6.9 μM. A decrease in reduced glutathione (GSH; 31%) levels, as well as an increase in oxidized glutathione (GSSG, 20%) was observed. In the presence of BEA, reactive oxygen species (ROS) level was highly increased at an early stage with the highest production of 2.0-fold higher than the control that was observed at 120 min. BEA induced cell death by mitochondria-dependent apoptotic process with loss of the mitochon…

Interaction effects of Fusarium enniatins (A, A1, B and B1) combinations on in vitro cytotoxicity of Caco-2 cells

Abstract Foodstuff is usually contaminated by more than one mycotoxin, however toxicological data are lacking as regards the effects in combinations compared to their individual effect. This study investigated the in vitro effects of enniatins (ENs) A, A1, B and B1, alone and in combinations, on Caco-2 cells viability by MTT assay after 24 h of exposure. Cells were treated with concentrations ranging from 0.9 to 15.0 μM, individually and in combination of two, three and four mycotoxins. Dose–response curves were generated for each mycotoxin and the isobologram method was used to determine the interactive effects of tested mixtures. Tested ENs produced significant cytotoxic effects both indi…

Effect of polyphenols on enniatins-induced cytotoxic effects in mammalian cells

Enniatins (ENs) are fungal secondary metabolites produced by genus Fusarium. The ENs exert antimicrobial and insecticidal effect, and has also been demonstrated cytotoxic effects on several mammalian cell lines. On the other hands, it has been proved that natural polyphenols have antioxidant effect. In this study, cell effects at low levels of exposure of four ENs (A, A(1), B and B(1)) and five polyphenols (quercetin, quercetin-3-β-D-glucoside, rutin, myricetin and t-pterostilbene) present in wine; and the cytoprotective effect of these polyphenols exposed simultaneously with ENs in Chinese Hamster Ovary (CHO-K1) cells, were studied. Cell effects were determined by the MTT test after 24 h o…

Reactive oxygen species involvement in apoptosis and mitochondrial damage in Caco-2 cells induced by enniatins A, A1, B and B1

The cytotoxic effects, the generation of reactive oxygen species (ROS) and lipid peroxidation (LPO) as well as the cell cycle disruption, the induction of apoptosis and changes in mitochondrial membrane potential (ΔΨm) as a function of increasing time have been determined in human colorectal adenocarcinoma (Caco-2) cells after exposure to enniatins (ENs) A, A₁, B and B₁. IC₅₀ values obtained by the MTT and Neutral Red assay, after 24, 48 and 72 h of exposure ranged from 0.5±0.1 to >15 μM. A significant increase (p≤0.05) in ROS generation and LPO production, as determined by the fluorescent probe H2-DCFDA and TBARS method respectively, was observed for all mycotoxins tested at 3.0 μM concent…

Cytotoxicity, biaccessibility and transport by Caco-2 cells of enniatins and beauvericin