Next Article in Journal
Variation of Fusarium Free, Masked, and Emerging Mycotoxin Metabolites in Maize from Agriculture Regions of South Africa
Next Article in Special Issue
Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?
Previous Article in Journal
Human Biomonitoring of Mycotoxins in Blood, Plasma and Serum in Recent Years: A Review
Previous Article in Special Issue
T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes
Open AccessArticle

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

1
Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technicka 3, 16628 Prague 6, Czech Republic
2
Department of Food Analysis and Nutrition, University of Chemistry and Technology, Technicka 3, 16628 Prague 6, Czech Republic
3
First Faculty of Medicine, Charles University, Katerinska 32, 12108 Prague 2, Czech Republic
4
Faculty General Hospital, U Nemocnice 2, 12808 Praha 2, Czech Republic
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(3), 148; https://doi.org/10.3390/toxins12030148
Received: 30 December 2019 / Revised: 21 February 2020 / Accepted: 25 February 2020 / Published: 28 February 2020
(This article belongs to the Special Issue Toxicological Effects of Mycotoxin on Target Cells)
Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration. View Full-Text
Keywords: acute toxicity; combined toxicity; genotoxicity; cell protection; silibinin; in silico prediction; co-culture models acute toxicity; combined toxicity; genotoxicity; cell protection; silibinin; in silico prediction; co-culture models
Show Figures

Figure 1

MDPI and ACS Style

Tran, V.N.; Viktorova, J.; Augustynkova, K.; Jelenova, N.; Dobiasova, S.; Rehorova, K.; Fenclova, M.; Stranska-Zachariasova, M.; Vitek, L.; Hajslova, J.; Ruml, T. In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment. Toxins 2020, 12, 148.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop