fusarenon-x and 3-acetyldeoxynivalenol

Type B trichothecenes commonly contaminate cereal grains and include five structurally related congeners: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), and nivalenol (NIV). These toxins are known to have negative effects on human and animal health, particularly affecting food intake. However, the pathophysiological basis for anorexic effect is not fully clarified. The purpose of this study is to explore the potential roles of the brain-gut peptides substance P (SP) and glucagon-like peptide-1

Topics: Amides; Animals; Anorexia; Appetite Depressants; Glucagon-Like Peptide 1; Humans; Substance P; Trichothecenes; Trichothecenes, Type B

Exposure to environmental contaminants might play an important role in neurodegenerative disease pathogenesis, such as Parkinson´s disease (PD) and Alzheimer´s disease (AD). For the first time in Spain, the plasmatic levels of 19 mycotoxins from patients diagnosed with a neurodegenerative disease (44 PD and 24 AD) and from their healthy companions (25) from La Rioja region were analyzed. The studied mycotoxins were aflatoxins B1, B2, G1, G2 and M1, T-2 and HT-2, ochratoxins A (OTA) and B (OTB), zearalenone, sterigmatocystin (STER), nivalenol, deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, deepoxy-deoxynivalenol, neosolaniol, diacetoxyscirpenol and fusarenon-X. Samples were analyzed by LC-MS/MS before and after treatment with β-glucuronidase/arylsulfatase in order to detect potential metabolites. Only OTA, OTB and STER were detected in the samples. OTA was present before (77% of the samples) and after (89%) the enzymatic treatment, while OTB was only detectable before (13%). Statistically significant differences in OTA between healthy companions and patients were observed but the observed differences might seem more related to gender (OTA levels higher in men,

Topics: Alzheimer Disease; Biological Monitoring; Chromatography, Liquid; Humans; Mycotoxins; Neurodegenerative Diseases; Ochratoxins; Parkinson Disease; Sterigmatocystin; Tandem Mass Spectrometry; Trichothecenes; Zearalenone

A reliable and sensitive analytical method was developed for simultaneous determination of deoxynivalenol(DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FUS-X), and masked deoxynivalenol (deoxynivalenol-3-glucoside, D3G) in formula feed, concentrated feed, and premixed feed products. The method was based on an improved sample pretreatment with the commercially available HLB cartridges used for sample purification and enrichment followed by analysis using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Several key parameters including the extraction solvents, the positions of sample loading solvents, washing and elution solvents for HLB cartridges were carefully optimized to achieve optimal extraction and purification efficiencies. The established method was extensively validated by determining the linearity (R² ≥ 0.99), sensitivity (limit of quantification in the range of 0.08-4.85 μg/kg), recovery (79.3%-108.1%), precision (Intra-day RSDs ≤ 13.5% and Inter-day RSDs ≤ 14.9%), and then was successfully applied to determine the four type B trichothecenes and D3G in a total of 31 feed samples. Among them, 26 were contaminated with various mycotoxins at the levels of 2.1-864.5 μg/kg, and D3G has also been detected in 17 samples with the concentrations in the range of 2.1-34.8 μg/kg, proving the established method to be a valuable tool for type B trichothecenes and masked DON monitoring in complex feed matrices.

Topics: Chromatography, Liquid; Food Analysis; Glucosides; Humans; Mycotoxins; Tandem Mass Spectrometry; Trichothecenes

In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly sensitive to mycotoxins. The aim of this study was to investigate the effects of deoxynivalenol (DON) and four other type B trichothecenes (TCTB), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX) alone or in combination on intestinal epithelial cells. Proliferating, non-transformed IPEC-1 cells were exposed to increasing doses of TCTB, alone or in binary mixtures and mycotoxin-induced cytotoxicity was measured with MTT test. The toxicological interactions were assessed using the isobologram-Combination index method. The five tested mycotoxins and their mixtures had a dose-dependent effect on the proliferating enterocytes. DON-NIV, DON-15-ADON and 15-ADON-3-ADON combinations were synergistic, with magnitude of synergy for 10 % cytotoxicity ranging from 2 to 7. The association between DON and 3-ADON also demonstrated a synergy but only at high doses, at lower doses antagonism was noted. Additivity was observed between NIV and FX, and antagonism between DON and FX. These results indicate that the simultaneous presence of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of TCTB in the diet.

Topics: Animals; Cell Culture Techniques; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; Epithelial Cells; Intestinal Mucosa; Swine; Trichothecenes

Cereal grain contamination by trichothecene mycotoxins is known to negatively impact human and animal health with adverse effects on food intake and growth being of particular concern. The head blight fungus Fusarium graminearum elaborates five closely related 8-ketotrichothecene congeners: (1) deoxynivalenol (DON), (2) 3-acetyldeoxynivalenol (3-ADON), (3) 15-acetyldeoxynivalenol (15-ADON), (4) fusarenon X (FX), and (5) nivalenol (NIV). While anorexia induction in mice exposed intraperitoneally to DON has been linked to plasma elevation of the satiety hormones cholecystokinin (CCK) and peptide YY₃₋₃₆ (PYY₃₋₃₆), the effects of oral gavage of DON or of other 8-keotrichothecenes on release of these gut peptides have not been established. The purpose of this study was to (1) compare the anorectic responses to the aforementioned 8-ketotrichothecenes following oral gavage at a common dose (2.5 mg/kg bw) and (2) relate these effects to changes plasma CCK and PYY₃₋₃₆ concentrations. Elevation of plasma CCK markedly corresponded to anorexia induction by DON and all other 8-ketotrichothecenes tested. Furthermore, the CCK1 receptor antagonist SR 27897 and the CCK2 receptor antagonist L-365,260 dose-dependently attenuated both CCK- and DON-induced anorexia, which was consistent with this gut satiety hormone being an important mediator of 8-ketotrichothecene-induced food refusal. In contrast to CCK, PYY₃₋₃₆ was moderately elevated by oral gavage with DON and NIV but not by 3-ADON, 15-ADON, or FX. Taken together, the results suggest that CCK plays a major role in anorexia induction following oral exposure to 8-ketotrichothecenes, whereas PYY₃₋₃₆ might play a lesser, congener-dependent role in this response.

Topics: Administration, Oral; Animals; Anorexia; Chemokines, CC; Cholecystokinin; Female; Mice; Mycotoxins; Peptide Fragments; Peptide YY; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Trichothecenes

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DON

Topics: Algorithms; Caco-2 Cells; Cell Survival; Coloring Agents; Dose-Response Relationship, Drug; Drug Synergism; Epithelial Cells; Humans; Intestinal Mucosa; Mycotoxins; Tetrazolium Salts; Thiazoles; Trichothecenes

A reliable and sensitive method for rapid simultaneous determination of two type A (T-2 and diacetoxyscirpenol) and two type B (3-acetyldeoxynivalenol and Fusarenon X) trichothecenes was developed and successfully applied for detecting trichothecenes in potato tubers by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry. The established method was further evaluated by determining the linearity (R ≥ 0.9995), recovery (113.28-77.97%), precision (relative standard deviation ≤ 5.89), and sensitivity (limit of detection, 0.002-0.005 μg/g; limit of quantitation, 0.005-0.015 μg/g). The method proved to be suitable for simultaneous determination of T-2, diacetoxyscirpenol, 3-acetyldeoxynivalenol, and Fusarenon X in potato tubers inoculated with Fusarium sulphureum . In addition, it was found that T-2, diacetoxyscirpenol, 3-acetyldeoxynivalenol, and Fusarenon X could be predominantly detected in the lesion, and the toxin could also be identified in tubers without any disease symptoms. The experimental results also indicated that the concentration of toxin in the susceptible cultivar (Longshu No. 3) was significantly higher than that in the resistant cultivar (Longshu No. 6).

Topics: Chromatography, High Pressure Liquid; Food Contamination; Food Inspection; Fusarium; Limit of Detection; Plant Immunity; Plant Tubers; Solanum tuberosum; Spectrometry, Mass, Electrospray Ionization; T-2 Toxin; Tandem Mass Spectrometry; Trichothecenes

Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON or vomitoxin), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV) in the mink emesis model following intraperitoneal (ip) and oral administration. All five congeners dose-dependently induced emesis by both administration methods. With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events. The effective doses resulting in emetic events in 50% of the animals for ip exposure to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 µg/kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 µg/kg bw, respectively. The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity. The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable. From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Male; Mice; Mink; Mycotoxins; Pica; Toxicity Tests; Trichothecenes; Vomiting

While induction of food refusal by the trichothecene mycotoxin deoxynivalenol (DON) has been described in several animal models, much less is known about the anorectic effects of structurally related 8-ketotrichothecenes, 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX) and nivalenol (NIV). Here, we compared the capacities of these congeners to induce anorexia in the mouse. As previously observed for DON, anorectic responses to 3-ADON and 15-ADON in the B6C3F1 female mouse following both intraperitoneal (IP) and oral exposure were transient, lasting only a few hours, with food intake recovering to control levels within 16 h. For both ADONs, the no observed adverse effect levels (NOAEL) and lowest observed adverse effect levels (LOAEL) were 0.5 and 1mg/kg bw following IP exposure, respectively, and 1 and 2.5mg/kg bw after oral exposure, respectively. In contrast, food refusal persisted from 48 to 96 h following IP and oral exposure to FX and NIV. For both IP and oral FX exposure, the NOAEL was 0.025 mg/kg bw and LOAEL was 0.25mg/kg bw, whereas the NOAELs and LOAELs for NIV were 0.01 and 0.1mg/kg bw, respectively, after IP exposure and 0.1 and 1mg/kg bw, respectively, following oral exposure. Both these data and a prior DON study suggest that anorectic responses to 8-ketotrichothecenes were always greater when administered IP as compared to oral exposure and follow an approximate rank order of NIV>FX>DON≈3-ADON≈15-ADON for IP exposure and FX>NIV>DON≈3-ADON≈15-ADON for oral exposure. Toxic potency data such as is described here will be applicable to future comparative risk assessments for this important group of trichothecene mycotoxins.

Topics: Animals; Appetite Depressants; Dose-Response Relationship, Drug; Eating; Female; Fusarium; Mice; Mice, Inbred Strains; Mycotoxins; No-Observed-Adverse-Effect Level; Trichothecenes

The objective of the present study was to monitor the occurrence and distribution of a spectrum of trichothecene toxins in different parts of maize plants. Therefore maize plants were sampled randomly from 13 fields in southwest Germany and the fractions kernels, cobs, husks, stalks, leaves and rudimentary ears were analyzed for eight A-type and five B-type trichothecenes. Each of the toxins was found in at least three of the total of 78 samples. The study revealed that both A-type and B-type trichothecenes may be present in all parts of the maize plant but may be unevenly distributed. For the contents of deoxynivalenol, 3- and 15-acetyldeoxynivalenol, nivalenol, scirpentriol, 15-monoacetoxyscirpenol, HT-2 and T-2 toxin significant differences (p < 0.05) were found between different parts of the maize plants whereas no significant differences were observed for fusarenon-X, 4,15-diacetoxyscirpenol, neosolaniol, T-2 triol and T-2 tetraol. Up to twelve toxins co-occurring in one sample were detected. As a group B-type trichothecenes dominated over A-type trichothecenes concerning incidences and levels. Contamination was strongest with rudimentary ears based on incidence and mean and maximum contents; mean contents with few exceptions tended towards a higher level than in other fractions with significant (p < 0.05) differences compared to leaves for seven toxins.

Topics: Food Contamination; Food Microbiology; Germany; T-2 Toxin; Trichothecenes; Zea mays

Fusarium graminearum is the most important pathogen causing Fusarium head blight (FHB) of small cereal grains worldwide responsible for quantitative and qualitative yield losses. The presence in crops is often associated with mycotoxin contamination of foodstuff limiting its use for human and animal consumption. A collection of isolates of F. graminearum from Germany was characterized genetically and chemically for their potential to produce the B trichothecenes deoxynivalenol (DON) and nivalenol (NIV). Molecular methods with eight PCR assays were implemented based on functional Tri7 and Tri13 genes and on the tri5-tri6 intergenic region to differentiate between chemotaxonomic groups DON and NIV, resulting in a marked majority (61/63) of DON chemotypes. Mycotoxins produced on rice kernels were quantified by means of LC-MSMS including DON, NIV, 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON), DON-3-glucoside, fusarenon X, as well as zearalenone; all of them proving to be present in high concentration among the isolates. All DON-chemotype isolates also produced lower amounts of NIV with the amount being positively correlated (R²=0.89) to the DON amount. 15-ADON and 3-ADON are reported to be produced simultaneously by the isolates, the former dominating over the latter in all but one isolate. Fungal biomass, was quantified via ergosterol amount on rice. It was used to calculate specific mycotoxin production per biomass of isolates, ranging from 0.104 to 1.815mg DON mg-1 ergosterol, presenting a Gaussian distribution. Genotype and phenotype characterization revealed discrepancies with respect to mycotoxin production potential of the fungi, i.e. isolates from one chemotype were able to produce mycotoxins from other chemotypes in considerable amounts.

Topics: DNA, Fungal; Ergosterol; Fusarium; Genotype; Germany; Glucosides; Oryza; Phenotype; Polymerase Chain Reaction; Trichothecenes; Zearalenone

A speedy and selective ultra-HPLC-MS/MS method for simultaneous determination of deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-ADON, nivalenol and fusarenon X in traditional Chinese medicines (TCMs) was developed. The method was based on one-step sample cleanup using reliable homemade cleanup cartridges. A linear gradient mobile-phase system, consisting of water containing 0.2% aqueous ammonia and acetonitrile/methanol (90:10, v/v) at a flow rate of 0.4 mL/min, and an Acquity UPLC HSS T3 column (100 mm x 2.1 mm, 1.8 microm) were employed to obtain the best resolution of the target analytes. [(13)C(15)]-DON was used as the internal standard to accomplish as accurate as possible quantitation. The established method was further validated by determining the linearity (R(2) > or = 0.9990), sensitivity (LOQ, 0.29-0.99 microg/kg), recovery (88.5-119.5%) and precision (RSD < or = 15.8%). It was shown to be a suitable method for simultaneous determination of DON, 3-ADON, 15-ADON, nivalenol and fusarenon X in various TCM matrices. The utility and practical impact of the method was demonstrated using different TCM samples.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Medicine, Chinese Traditional; Molecular Conformation; Stereoisomerism; Tandem Mass Spectrometry; Trichothecenes