Mycotoxins can cause body poisoning and induce carcinogenesis, often with a high mortality rate. Therefore, it is of great significance to seek new targets that indicate mycotoxin activity and to diagnose and intervene in mycotoxin-induced diseases in their early stages. MicroRNAs (miRNAs) are physiological regulators whose dysregulation is closely related to the development of diseases. They are thus important markers for the occurrence and development of diseases. In this review, consideration is given to the toxicological mechanisms associated with four major mycotoxins (ochratoxin A, aflatoxin B1, deoxynivalenol, and zearalenone). The roles that miRNAs play in these mechanisms and the interactions between them and their target genes are explained, and summarize the important role of histone modifications in their toxicity. As a result, the ways that miRNAs are regulated in the pathogenicity signaling pathways are revealed which highlights the roles played by miRNAs in preventing and controlling the harmful effects of the mycotoxins. It is hoped that this review will provide a theoretical basis for the prevention and control of the damage caused by these mycotoxins.

• Klíčová slova
• Histone, Methylation, MicroRNA, Mycotoxin,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The consumption of herbal-based supplements, which are believed to have beneficial effects on human health with no side effects, has become popular around the world and this trend is still increasing. Silybum marianum (L.) Gaertn, commonly known as milk thistle (MT), is the most commonly studied herb associated with the treatment of liver diseases. The hepatoprotective effects of active substances in silymarin, with silybin being the main compound, have been demonstrated in many studies. However, MT can be affected by toxigenic micro-fungi and contaminated by mycotoxins with adverse effects. The beneficial effect of silymarin can thus be reduced or totally antagonized by mycotoxins. MT has proven to be affected by micro-fungi of the Fusarium and Alternaria genera, in particular, and their mycotoxins. Alternariol-methyl-ether (AME), alternariol (AOH), beauvericin (BEA), deoxynivalenol (DON), enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), HT-2 toxin (HT-2), T-2 toxin (T-2), tentoxin (TEN), and zearalenone (ZEA) seem to be most significant in MT-based dietary supplements. This review focuses on summarizing cases of mycotoxins in MT to emphasize the need for strict monitoring and regulation, as mycotoxins in relation with MT-based dietary supplements are not covered by European Union legislation.

• Klíčová slova
• food supplements, liver diseases, milk thistle, mycotoxins, silymarin,
• MeSH
• Evropská unie MeSH
• lidé MeSH
• mykotoxiny škodlivé účinky   analýza   MeSH
• ostropestřec mariánský škodlivé účinky   MeSH
• potravní doplňky škodlivé účinky   analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mykotoxiny MeSH

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.

• Klíčová slova
• acute toxicity, cell protection, co-culture models, combined toxicity, genotoxicity, in silico prediction, silibinin,
• MeSH
• buněčné linie MeSH
• kokultivační techniky MeSH
• kometový test MeSH
• lékové interakce MeSH
• lidé MeSH
• mykotoxiny toxicita   MeSH
• myši MeSH
• ochranné látky farmakologie   MeSH
• ostropestřec mariánský chemie   MeSH
• P-glykoprotein metabolismus   MeSH
• počítačová simulace MeSH
• potravní doplňky MeSH
• silibinin farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mykotoxiny MeSH
• ochranné látky MeSH
• P-glykoprotein MeSH
• silibinin MeSH