A Two-Year Occurrence of Fusarium T-2 and HT-2 Toxin in Croatian Cereals Relative of the Regional Weather.

To investigate into the T-2 and HT-2 toxin occurrence, 240 samples of unprocessed cereals (maize, wheat, barley, and oats) were sampled from different fields located in three Croatian regions during 2017-2018. In all samples, sum concentrations of T-2/HT-2 toxin were determined using the ELISA method, while the LC-MS/MS was used as a confirmatory method for both mycotoxins in positive samples (>LOD) and the establishment of T-2 over HT-2 toxin ratios. The results showed oats to be the most contaminated cereal, with T-2/HT-2 toxins detected in 70.0% of samples, followed by barley (40.9%), maize (26.8%) and wheat (19.2%), with the mean T-2/HT-2 ratio ranging from 1:2.7 in maize to 1:4.4 in oats. Sum T-2/HT-2 concentrations in two maize samples were higher than the indicative level recommended by the European Commission, necessitating subsequent investigations into the conditions under which these poorly investigated mycotoxins are produced. Statistically significantly (p < 0.05) higher concentrations of T-2/HT-2 toxin were determined in oats throughout study regions as compared to those found in wheat, but not maize and barley, while the concentrations of these mycotoxins were related to the regional weather in Croatia.

Preparation of T­2 toxin­containing pH­sensitive liposome and its antitumor activity.

T­2 toxin is a type A trichothecene mycotoxin. In order to reduce the side effects of T­2 toxin and increase the tumor targeting ability, a pH­sensitive liposome of T­2 toxin (LP­pHS­T2) was prepared and characterized in the present study. The cytotoxicity of LP­pHS­T2 on A549, Hep­G2, MKN­45, K562 and L929 cell lines was tested by 3­(4,5­dimethylthiazolyl­2)­2,5­diphenyltetrazolium bromide assay, with T­2 toxin as the control. The apoptotic and migratory effects of LP­pHS­T2 on Hep­G2 cells were investigated. The preparation process of LP­pHS­T2 involved the following parameters: Dipalmitoyl phosphatidylcholine: dioleoylphosphatidylethanolamine, 1:2; total phospholipid concentration, 20 mg/ml; phospholipid:cholesterol, 3:1; 4­(2­hydroxyethyl)­1­piperazineethanesulfonic acid buffer (pH 7.4), 10 ml; drug:lipid ratio, 2:1; followed by ultrasound for 10 min and extrusion. The encapsulation efficiency reached 95±2.43%. The average particle size of LP­pHS­T2 after extrusion was 100 nm; transmission electron microscopy showed that the shape of LP­pHS­T2 was round or oval and of uniform size. The release profile demonstrated a two­phase downward trend, with fast leakage of T­2 toxin in the first 6 h (~20% released), followed by sustained release up to 48 h (~46% released). From 48­72 h, the leakage rate increased (~76% released), until reaching a minimum at 72 h. When LP­pHS­T2 was immersed in 0.2 mol/l disodium phosphate­sodium dihydrogen phosphate buffers (pH 6.5), the release speed was significantly increased and the release rate reached 91.2%, demonstrating strong pH sensitivity. Overall, antitumor tests showed that LP­pHS­T2 could promote the apoptosis and inhibit the migration of Hep­G2 cells. The present study provided a new approach for the development of T­2 toxin­based anti­cancer drugs.

Co-Occurrence of Moniliformin and Regulated Fusarium Toxins in Maize and Wheat Grown in Italy.

The co-occurrence of moniliformin (MON), fumonisins (FBs), and deoxynivalenol (DON) was evaluated in maize, durum, and common wheat grown in different experimental fields located in several Italian regions. MON was quantified using a LC-MS/MS method adding lanthanum ions in the mobile phase. In maize, MON contamination was widespread and considerable; the toxin was detected in almost all the samples (95.1%) and exceeded 500 and 1000 µg kg-1 in 42.0% and in 18.5% of samples, respectively. Significant positive correlation was found between MON and FB contamination levels. When there were not droughty climate conditions, a positive significant correlation was found between growing degree days (GDD) and MON values. In wheat, MON contamination was not widespread like in maize and it was lower in common wheat than in durum wheat. In durum wheat, MON was detected in 45.0% of the samples with only 6 samples (7.5%) exceeding 500 µg kg-1, while in common wheat the toxin was detected above the LOD in 18.7% of samples exceeding 100 µg kg-1 in only two samples (2.5%). No correlation was found with DON contamination. Climate conditions influenced both MON and DON occurrence.

Intestinal Metabolism of α- and ß-Glucosylated Modified Mycotoxins T-2 and HT-2 Toxin in the Pig Cecum Model.

The type A trichothecene mycotoxins T-2 and HT-2 toxin are fungal secondary metabolites produced by Fusarium fungi, which contaminate food and feed worldwide. Especially as a result of the high toxicity of T-2 toxin and their occurrence together with glucosylated forms in cereal crops, these mycotoxins are of human health concern. Particularly, it is unknown whether and how these modified mycotoxins are metabolized in the gastrointestinal tract and, thus, contribute to the overall toxicity. Therefore, the comparative intestinal metabolism of T-2 and HT-2 toxin glucosides in α and ß configuration was investigated using the ex vivo pig cecum model, which mimics the human intestinal metabolism. Regardless of its configuration, the C-3 glycosidic bond was hydrolyzed within 10-20 min, releasing T-2 and HT-2 toxin, which were further metabolized to HT-2 toxin and T-2 triol, respectively. We conclude that T-2 and HT-2 toxin should be evaluated together with their modified forms for risk assessment.

Individual and combined cytotoxic effects of T-2 toxin and its four metabolites on porcine Leydig cells.

T-2 toxin, one of the most toxic mycotoxins, is commonly presented along with its metabolites, HT-2 toxin, neosolaniol (NEO), T-2 triol, and T-2 tetraol in foodstuff and feed. The aim of this study was to evaluate the cytotoxic effects of T-2 toxin alone and in combination with its metabolites on porcine Leydig cells. Based on the determination of cell viability with CCK-8, toxicological interactions were investigated using Combination Index method. The cytotoxic potency of five tested mycotoxins individual and their mixtures all showed with a dose-dependent manner. In view of IC50 values, the decreasing cytotoxicity of mycotoxins was ranking: T-2 toxin > HT-2 toxin > T-2 triol > NEO > T-2 tetraol. Combinations of T-2+HT-2, T-2+NEO, and HT-2+NEO displayed synergism at low doses but antagonism at high doses, while the ternary combination of T-2+HT-2+NEO revealed adverse situation from antagonism to synergism. All binary and ternary combinations of T-2 toxin, T-2 triol, and T-2 tetraol exhibited antagonistic interactions. Our results suggest that the co-occurrence of T-2 toxin and its metabolites might pose a slight threat to reproductive health due to antagonistic interactions. However, the synergy observed should be not ignored especially at low doses of mycotoxins co-occurrence in the diet.

Efficacy of low pressure DBD plasma in the reduction of T-2 and HT-2 toxin in oat flour.

T-2 and its major metabolite HT-2 toxin are naturally occurring contaminants in cereals, with the highest concentrations determined in oats. Because of their toxicity and resistance to conventional methods used in mycotoxin degradation, development of new effective procedures for reduction of T-2/HT-2 toxin levels is needed. The aim of this study was to investigate the effect of different gas types within various timeframes on the efficiency of T-2 and HT-2 toxin degradation by low pressure dielectric barrier discharge (DBD) plasma in oat flour. Although humidity of the sample influences the intensity of the plasma, oxygen atoms efficiently oxidize the sample and produce CO and N2. Before and after treatment, T-2 and HT-2 toxin concentrations were analysed by the confirmatory liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. The highest reduction of T-2 and HT-2 toxin of 43.25% and 38.54%, respectively, was achieved using nitrogen plasma and this proved to be time-dependent.

Decontamination of T-2 Toxin in Maize by Modified Montmorillonite Clay.

Montmorillonite clay has a wide range of applications, one of which includes the binding of mycotoxins in foods and feeds through adsorption. T-2 toxin, produced by some Fusarium, Myrothecium, and Stachybotrys species, causes dystrophy in the brain, heart, and kidney. Various formulations that include lemongrass essential oil-modified montmorillonite clay (LGEO-MMT), lemongrass powder (LGP), montmorillonite clay washed with 1 mM NaCl (Na-MMT), montmorillonite clay (MMT), and lemongrass powder mixed with montmorillonite clay (LGP-MMT) were applied to maize at concentrations of 8% and 12% and stored for a period of one month at 30 °C. Unmodified montmorillonite clay and LGP served as the negative controls alongside untreated maize. Fourier Transform Infrared (FTIR) spectra of the various treatments showed the major functional groups as Si-O and -OH. All treatment formulations were effective in the decontamination of T-2 toxin in maize. Accordingly, it was revealed that the inclusion of Na-MMT in maize at a concentration of 8% was most effective in decontaminating T-2 toxin by 66% in maize followed by LGP-MMT at 12% inclusion level recording a 56% decontamination of T-2 toxin in maize (p = 0.05). Montmorillonite clay can be effectively modified with plant extracts for the decontamination of T-2 toxin.

A novel sandwich aptasensor for detecting T-2 toxin based on rGO-TEPA-Au@Pt nanorods with a dual signal amplification strategy.

T-2 toxin is a mycotoxin that can cause chronic illnesses, and the detection of T-2 toxin in food is critical for human health. Herein, a novel sandwich aptasensor with a dual signal amplification strategy was developed for the detection of T-2 toxin. Molybdenum disulfide-polyaniline-chitosan-gold nanoparticles (MoS2-PANI-Chi-Au) were processed to the modified glassy carbon electrode (GCE) and used as the aptasensor platform to expedite the electronics transport and immobilize the amino-terminated capture DNA probe by Au-N bonds. The reduced graphene oxide-tetraethylene pentamine-gold@platinum nanorods (rGO-TEPA-Au@Pt NRs) were first synthesized and immobilized with a signal DNA probe. Once T-2 toxin was added into the biosensing system, the aptamer would trap T-2 toxin to turn the signal off. Next, dissociative aptamer hybridized with the capture DNA probe in GCE and linked simultaneously to the signal DNA probe on rGO-TEPA-Au@Pt NRs with another end sequence of aptamer to turn the signal on. Owing to the efficient catalytic ability of bimetallic Au@Pt nanorods, the signal was perfectly amplified through the catalysis of hydrogen peroxide (H2O2) and recorded by chronoamperometry. With the outstanding augment response, the limit of detection reached 1.79 fg mL-1 (3SB/m) and a wide linear range from 10 fg mL-1 to 100 ng mL-1 was presented. The sensitivity of the aptasensor was 19.88 µA⋅µM-1⋅cm-2. Meanwhile, the DNA aptamer-bimetallic nanorod based sensing system presented excellent specificity. The developed aptasensor provides a new platform for T-2 toxin detection with low cost for real sample assays.

Combined Inhibitory Effects of Citrinin, Ochratoxin-A, and T-2 Toxin on Aquaporin-2.

Aquaporins form a large family of transmembrane protein channel that facilitates selective and fast water transport across the cell membrane. The inhibition of aquaporin channels leads to many water-related diseases such as nephrogenic diabetes insipidus, edema, cardiac arrest, and stroke. Herein, we report the molecular mechanism of mycotoxins (citrinin, ochratoxin-A, and T-2 mycotoxin) inhibition of aquaporin-2 (AQP2) and arginine vasopressin receptor 2. Molecular docking, molecular dynamics simulations, quantum chemical calculations, residue conservation-coupling analysis, sequence alignment, and in vivo studies were utilized to explore the binding interactions between the mycotoxins and aquaporin-2. Theoretical studies revealed that the electrostatic interactions induced by the toxins pulled the key residues (187Arg, 48Phe, 172His, and 181Cys) inward, hence reduced the pore diameter and water permeation. The permeability coefficient of the channel was reduced from native ((3.32 ± 0.75) × 10-14 cm3/s) to toxin-treated AQP2 ((1.08 ± 0.03) × 10-14 cm3/s). The hydrogen bonds interruption and formation of more hydrogen bonds with toxins also led to the reduced number of water permeation. Further, in vivo studies showed renal damages and altered level of aquaporin expression in mycotoxin-treated Mus musculus. Furthermore, the multiple sequence alignments among the model organism along with evolutionary coupling analysis provided the information about the interdependences of the residues in the channel.

A Novel Modified Hydrated Sodium Calcium Aluminosilicate (HSCAS) Adsorbent Can Effectively Reduce T-2 Toxin-Induced Toxicity in Growth Performance, Nutrient Digestibility, Serum Biochemistry, and Small Intestinal Morphology in Chicks.

The objective of this study was to evaluate the ability of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce the toxicity of T-2 toxin in broilers. Ninety-six one-day-old male broilers were randomly allocated into four experimental groups with four replicates of six birds each. The four groups, 1-4, received a basal diet (BD), a BD plus 6.0 mg/kg T-2 toxin, a BD plus 6.0 mg/kg T-2 toxin with 0.05% modified HSCAS adsorbent, and a BD plus 0.05% modified HSCAS adsorbent, respectively, for two weeks. Growth performance, nutrient digestibility, serum biochemistry, and small intestinal histopathology were analyzed. Compared to the control group, dietary supplementation of T-2 toxin decreased (p < 0.05) body weight gain, feed intake, and the feed conversion ratio by 11.4%-31.8% during the whole experiment. It also decreased (p < 0.05) the apparent metabolic rates of crude protein, calcium, and total phosphorus by 14.9%-16.1%. The alterations induced by T-2 toxin were mitigated (p < 0.05) by the supplementation of the modified HSCAS adsorbent. Meanwhile, dietary modified HSCAS adsorbent supplementation prevented (p < 0.05) increased serum aspartate aminotransferase by T-2 toxin at d 14. It also prevented (p < 0.05) T-2 toxin-induced morphological changes and damage in the duodenum, jejunum, and ileum of broilers. However, dietary supplementation of the modified HSCAS adsorbent alone did not affect (p > 0.05) any of these variables. In conclusion, these findings indicate that the modified HSCAS adsorbent could be used against T-2 toxin-induced toxicity in growth performance, nutrient digestibility, and hepatic and small intestinal injuries in chicks.

Biological Toxins as the Potential Tools for Bioterrorism.

Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as "Chemicals produced by living organisms that have toxic properties for another organism". Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD50 < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, Clostridium perfringens toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins.

Matrix binding of T-2 toxin: structure elucidation of reaction products and indications on the fate of a relevant food-borne toxin during heating.

This study deals with the influence of food matrix components on the degradation of the mycotoxins T-2 toxin (T-2) and HT-2 toxin (HT-2) and with the binding of T-2 to starch during thermal food processing. Both mycotoxins were heated in a simulated food environment and subsequently analyzed via HPLC-HRMS to generate degradation curves and to draw conclusions regarding the thermal degradation under food processing conditions. Thermal degradation increased generally with increasing time and temperature with a maximum degradation rate of 93% (T-2) and 99% (HT-2). Furthermore, HRMS data were exploited to screen the samples for degradation products. In model heating experiments, T-2 was bound to 1-O-methyl-α-D-glucopyranoside, a model compound that was used to simulate starch. The formed reaction products were isolated and identified by NMR, giving detailed insights into a potential binding of T-2 to starch. In the next step, further model heating experiments were performed, which proved the covalent binding of T-2 to starch. Finally, the amount of matrix-bound T-2 was estimated roughly in a semi-quantitative approach in the model heating experiments as well as during cookie-making via GC-MS analysis of the isovaleric acid ester moiety of T-2, released after alkaline hydrolysis.

Thermal stability of T-2 and HT-2 toxins during biscuit- and crunchy muesli-making and roasting.

The mycotoxins T-2 and HT-2 toxin are frequently occurring food contaminants which are produced by Fusarium species. Humans and animals are mainly exposed to these substances by the consumption of contaminated oats, maize and wheat. For the production of crunchy muesli, bread and bakery products, these cereals undergo multiple processing steps, including baking, roasting and extrusion cooking. However, the influence of food processing on T-2 and HT-2 toxin levels is to date poorly understood. Thus, the effects of baking and roasting on both mycotoxins were evaluated during biscuit-, crunchy muesli- and toasted oat flakes-production under precise variation of various parameters: heating time and temperature as well as recipe formulation were varied in the range they are applied in the food processing industry. Therefore, oatmeal or flaked oats were artificially contaminated individually with both toxins and processed at the laboratory scale. T-2 toxin generally showed a higher degradation rate than HT-2 toxin. During biscuit-making up to 45% of T-2 toxin and 20% of HT-2 toxin were thermally degraded, showing a dependency on water content, baking time and temperature. The preparation of crunchy muesli yielded no significant toxin degradation which is probably due to the low temperatures applied. Roasting led to a degradation of 32% of T-2 toxin and 24% of HT-2 toxin. Taken together, both mycotoxins are partially degraded during thermal food processing; the degradation rates are influenced by the food composition and processing parameters.

Toxicokinetics of HT-2 Toxin in Rats and Its Metabolic Profile in Livestock and Human Liver Microsomes.

The lack of information on HT-2 toxin leads to inaccurate hazard evaluations. In the present study, toxicokinetic studies of HT-2 toxin were investigated following intravenous (iv) and oral administration to rats at dosages of 1.0 mg per kilogram of body weight. After oral administration, HT-2 toxin was not detected in plasma, whereas its hydroxylated metabolite, 3'-OH HT-2 was identified. Following iv administration, HT-2 toxin; its 3'-hydroxylated product; and its glucuronide derivative, 3-GlcA HT-2, were observed in plasma, and the glucuronide conjugate was the predominant metabolite. To explore the missing HT-2 toxin in plasma, metabolic studies of HT-2 toxin in liver microsomes were conducted. Consequently, eight phase I and three phase II metabolites were identified. Hydroxylation, hydrolysis, and glucuronidation were the main metabolic pathways, among which hydroxylation was the predominant one, mediated by 3A4, a cytochrome P450 enzyme. Additionally, significant interspecies metabolic differences were observed.

An Imaging Surface Plasmon Resonance Biosensor Assay for the Detection of T-2 Toxin and Masked T-2 Toxin-3-Glucoside in Wheat.

A sensitive, rapid, and reproducible imaging surface plasmon resonance (iSPR) biosensor assay was developed to detect T-2 toxin and T-2 toxin-3-glucoside (T2-G) in wheat. In this competitive assay, an amplification strategy was used after conjugating a secondary antibody (Ab2) with gold nanoparticles. Wheat samples were extracted with a methanol/water mixture (80:20 v/v), then diluted with an equal volume of primary antibody (Ab1) for analysis. Matrix-matched calibration curves were prepared to determine T-2 toxin and T2-G. Recovery studies were conducted at three spiking levels in blank wheat. Mean recoveries ranged from 86 to 90%, with relative standard deviations for repeatability (RSDr) of less than 6%. Limits of detection were 1.2 ng/mL of T-2 toxin and 0.9 ng/mL of T2-G, equivalent to their levels in wheat, of 48 and 36 µg/kg, respectively. The developed iSPR assay was rapid and provided enough sensitivity for the monitoring of T-2 toxin/T2-G in wheat. This is the first iSPR assay useful for detecting the "masked" T2-G in wheat.

Glucosylation of T-2 and HT-2 toxins using biotransformation and chemical synthesis: Preparation, stereochemistry, and stability.

Plant-derived phase II metabolites of T-2 toxin (T2) and HT-2 toxin (HT2) were first described in 2011 and further characterized in the following years. Since then, some efforts have been made to understand their biosynthesis, occurrence, toxicity, toxicokinetics, and finally relevance for consumers. Thus, the probably most important question is whether and how these metabolites contribute to toxicity upon hydrolysis either during food processing or the gastrointestinal passage. To answer this question, firstly, knowledge on the correct stereochemistry of T2 and HT2 glucosides is important as this affects hydrolysis and chemical behavior. So far, contradictory results have been published concerning the number and anomericity of occurring glucosides. For this reason, we set up different strategies for the synthesis of mg-amounts of T2, HT2, and T2 triol glucosides in both α and ß configuration. All synthesized glucosides were fully characterized by NMR spectroscopy as well as mass spectrometry and used as references for the analysis of naturally contaminated food samples to validate or invalidate their natural occurrence. Generally, 3-O-glucosylation was observed with two anomers of HT2 glucoside being present in contaminated oats. In contrast, only one anomer of T2 glucoside was found. The second aspect of this study addresses the stability of the glucosides during thermal food processing. Oat flour was artificially contaminated with T2 and HT2 glucosides individually and extruded at varying initial moisture content and temperature. All four glucosides appear to be more stable during food extrusion than the parent compounds with the glucosidic bond not being hydrolyzed.

T-2 Toxin-3α-glucoside in Broiler Chickens: Toxicokinetics, Absolute Oral Bioavailability, and in Vivo Hydrolysis.

Due to the lack of information on bioavailability and toxicity of modified mycotoxins, current risk assessment on these modified forms assumes an identical toxicity of the modified form to their respective unmodified counterparts. Crossover animal trials were performed with intravenous and oral administration of T-2 toxin (T-2) and T-2 toxin-3α-glucoside (T2-G) to broiler chickens. Plasma concentrations of T2-G, T-2, and main phase I metabolites were quantified using a validated liquid chromatography-tandem mass spectrometry method with a limit of quantitation for all compounds of 0.1 ng/mL. Resulting plasma concentration-time profiles were processed via two-compartmental toxicokinetic models. No T-2 triol and only traces of HT-2 were detected in the plasma samples after both intravenous and oral administration. The results indicate that T-2 has a low absolute oral bioavailability of 2.17 ± 1.80%. For T2-G, an absorbed fraction of the dose and absolute oral bioavailability of 10.4 ± 8.7% and 10.1 ± 8.5% were observed, respectively. This slight difference is caused by a minimal (and neglectable) presystemic hydrolysis of T2-G to T-2, that is, 3.49 ± 1.19%. Although low, the absorbed fraction of T2-G is 5 times higher than that of T-2. These differences in toxicokinetics parameters between T-2 and T2-G clearly indicate the flaw in assuming equal bioavailability and/or toxicity of modified and free mycotoxins in current risk assessments.

Impact of Mechanical and Thermal Energies on the Degradation of T-2 and HT-2 Toxins during Extrusion Cooking of Oat Flour.

The type A trichothecenes T-2 toxin (T-2) and HT-2 toxin (HT-2) are naturally occurring toxic food contaminants, with the highest concentrations found in contaminated oats. The influence of thermal food processing on these toxins is poorly understood, and only a few publications address the degradation rates. Therefore, we systematically investigated the degradation of T-2 and HT-2 during both laboratory and industrial-scale extrusion cooking of oats. Extrusion cooking under laboratory conditions was performed with oats fortified with T-2 or HT-2 as well as with naturally contaminated oat flour dust. The experiments were designed according to industrial conditions in terms of temperature, water content, pressure, residence time, and oat content. Flour mixtures containing naturally contaminated oats were used for industrial-scale processing. Degradation rates under laboratory conditions were up to 59.6 ± 1.51 and 47.2 ± 0.53% for T-2 and HT-2, respectively, in fortified extrudates but were decreased to 35.1 ± 1.55 and 22.0 ± 4.68% when naturally contaminated flour samples were used. The results show a higher degradation of T-2 during extrusion cooking than of HT-2. Moisture content, mechanical shear, and temperature showed an impact on the toxin degradation and can be optimized to counteract food contamination.

T-2 mycotoxin: toxicological effects and decontamination strategies.

Mycotoxins are highly diverse secondary metabolites produced in nature by a wide variety of fungus which causes food contamination, resulting in mycotoxicosis in animals and humans. In particular, trichothecenes mycotoxin produced by genus fusarium is agriculturally more important worldwide due to the potential health hazards they pose. It is mainly metabolized and eliminated after ingestion, yielding more than 20 metabolites with the hydroxy trichothecenes-2 toxin being the major metabolite. Trichothecene is hazardously intoxicating due to their additional potential to be topically absorbed, and their metabolites affect the gastrointestinal tract, skin, kidney, liver, and immune and hematopoietic progenitor cellular systems. Sensitivity to this type of toxin varying from dairy cattle to pigs, with the most sensitive endpoints being neural, reproductive, immunological and hematological effects. The mechanism of action mainly consists of the inhibition of protein synthesis and oxidative damage to cells followed by the disruption of nucleic acid synthesis and ensuing apoptosis. In this review, the possible hazards, historical significance, toxicokinetics, and the genotoxic and cytotoxic effects along with regulatory guidelines and recommendations pertaining to the trichothecene mycotoxin are discussed. Furthermore, various techniques utilized for toxin determination, pathophysiology, prophylaxis and treatment using herbal antioxidant compounds and regulatory guidelines and recommendations are reviewed. The prospects of the trichothecene as potential hazardous agents, decontamination strategies and future perspectives along with plausible therapeutic uses are comprehensively described.

In silico analysis sheds light on the structural basis underlying the ribotoxicity of trichothecenes-A tool for supporting the hazard identification process.

Deoxynivalenol is a food borne mycotoxin belonging to the trichothecenes family that may cause severe injuries in human and animals. The inhibition of protein synthesis via the interaction with the ribosome has been identified as a crucial mechanism underlying toxic action. However, it is not still fully understood how and to what extent compounds belonging to trichothecenes family affect human and animal health. In turn, this scenario causes delay in managing the related health risk. Aimed at supporting the hazard identification process, the in silico analysis may be a straightforward tool to investigate the structure-activity relationship of trichothecenes, finding out molecules of possible concern to carry forth in the risk assessment process. In this framework, this work investigated through a molecular modeling approach the structural basis underlying the interaction with the ribosome under a structure-activity relationship perspective. To identify further forms possibly involved in the total trichothecenes-dependent ribotoxic load, the model was challenged with a set of 16 trichothecene modified forms found in plants, fungi and animals, including also compounds never tested before for the capability to bind and inhibit the ribosome. Among them, only the regiospecific glycosylation in the position 3 of the sesquiterpenoid scaffold (i.e. T-2 toxin-3-glucuronide, α and ß isomers of T-2 toxin-3-glucoside and deoxynivalenol-3-glucuronide) was found impairing the interaction with the ribosome, while the other compounds tested (i.e. neosolaniol, nivalenol, fusarenon-X, diacetoxyscirpenol, NT-1 toxin, HT-2 toxin, 19- and 20-hydroxy-T-2 toxin, T-2 toxin triol and tetraol, and 15-deacetyl-T-2 toxin), were found potentially able to inhibit the ribosome. Accordingly, they should be included with high priority in further risk assessment studies in order to better characterize the trichothecenes-related hazard.