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). 3-AcDON was the most cytotoxic molecule in HepG2 cells. The concentrations tested in combinations ranged from 0.5625 to 4.5 µM (DON), and from 0.094 to 0.75 µM (DON derivatives), with ratios of 1:6 (DON+3-AcDON and DON+15-AcDON), 1:1 (3-AcDON+15-AcDON) and 1:6:6 (DON+3-AcDON+15-AcDON). The DON+15-AcDON mixture exhibited additive effects, while the rest showed synergistic effects. In silico methods assess individual mycotoxins. Absorption, Distribution, Metabolism, Excretion and Toxicity of mycotoxins were predicted using in silico SwissADME tools. Absorption, Distribution, Metabolism and Excretion profile prediction shows high gastrointestinal absorption and CYP3A4 mediated metabolism.

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 cells against oxidative stress produced by BEA. Despite its strong cytotoxicity, no risk assessment have been still carried out by authorities due to a lack of toxicity data, so research on BEA toxicological impact is still going on. This review reports information available regarding BEA mechanistic toxicology with the aim of updating information regarding last researches on this mycotoxin.

A Review of the Mycotoxin Enniatin B.

Mycotoxin enniatin B (ENN B) is a secondary metabolism product by Fusarium fungi. It is a well-known antibacterial, antihelmintic, antifungal, herbicidal, and insecticidal compound. It has been found as a contaminant in several food commodities, particularly in cereal grains, co-occurring also with other mycotoxins. The primary mechanism of action of ENN B is mainly due to its ionophoric characteristics, but the exact mechanism is still unclear. In the last two decades, it has been a topic of great interest since its potent mammalian cytotoxic activity was demonstrated in several mammalian cell lines. Moreover, the co-exposure in vitro with other mycotoxins enhances its toxic potential through synergic effects, depending on the concentrations tested. Despite its clear cytotoxic effect, European Food Safety Authority stated that acute exposure to ENNs, such as ENN B, does not indicate concern for human health, but a concern might be the chronic exposure. However, given the lack of relevant toxicity data, no firm conclusion could be drawn and a risk assessment was not possible. In fact, very few studies have been carried out in vivo and, in these studies, no adverse effects were observed. So, research on toxicological effects induced by ENN B is still on-going. Recently, some studies are dealing with new advances regarding ENN B. This review summarizes the information on biochemical and biological activity of ENN B, focusing on toxicological aspects and on the latest advances in research on ENN B.

Bioaccessibility of enniatins A, A1, B, and B1 in different commercial breakfast cereals, cookies, and breads of Spain.

Fusarotoxins enniatins (ENs) can represent a potential risk as natural contaminants of cereal commodities. However, only their bioaccessible fraction can exert a toxicity. The purpose of this study was to determine the ENs A, A1, B, and B1 bioaccessibility added in 1.5 and 3.0 µmol/g concentrations in breakfast cereals, cookies, and breads using a simulated in vitro gastrointestinal extraction model. Bioaccessibility values ranged between 40.4 ± 1.9 and 79.9 ± 2.8%. The lower values were 50.1, 40.4, 43.9, and 46.3% in wheat bran with fibers, and the higher values were 79.9, 64.2, 69.8, and 73.6% in white loaf bread for the ENs A, A1, B, and B1, respectively. Food composition, compounds structure, and presence of natural adsorbing materials can influence the ENs bioaccessibility. Application of a simulated in vitro gastrointestinal method is a good procedure to assess oral ENs bioaccessibility in cookies, breakfast cereals, and bread.