nsc-141537 and neosolaniol

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

Trichothecene mycotoxins commonly contaminate cereal grains and are often linked to human and animal food poisoning. The rapid onset of anorexia is a common hallmark of trichothecenes-induced toxicity. Although the neurotransmitters 5-hydroxytryptamine (5-HT) and substance P (SP) are known to regulate appetite, it remains unknown whether these two neurotransmitters are involved in type A trichothecenes-induced anorectic response. The goal of this study is to relate plasma 5-HT and SP to anorectic responses induced by type A trichothecenes T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS) and neosolaniol (NEO). These four toxins evoked robust anorectic response and secretion of plasma 5-HT and SP at 1 mg/kg bw. Following oral exposure, plasma 5-HT and SP were elevated and all peaked at 2 h for T-2, HT-2, DAS and NEO. Following intraperitoneal (IP) administration, plasma 5-HT and SP were peaked at 6 h, 6 h, 2 h, 2 h and 2 h, 6 h, 2 h, 2 h for T-2, HT-2, DAS and NEO, respectively. Elevations of plasma 5-HT and SP markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Altogether, the results presented herein indicated that 5-HT and SP play contributory roles in anorectic responses induced by T-2, HT-2, DAS and NEO.

Topics: Animals; Anorexia; Appetite Depressants; Edible Grain; Female; Mice; Neurotransmitter Agents; Serotonin; Substance P; T-2 Toxin; Trichothecenes

Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia.

Topics: Animals; Anorexia; Female; Gastric Inhibitory Polypeptide; Mice; Mycotoxins; Peptide Fragments; Peptide YY; T-2 Toxin; Trichothecenes

Topics: Animals; Anorexia; Appetite Regulation; Behavior, Animal; Cholecystokinin; Disease Models, Animal; Feeding Behavior; Female; Glucagon-Like Peptide 1; Mice; Peptide Fragments; Satiety Response; Signal Transduction; T-2 Toxin; Time Factors; Trichothecenes; Up-Regulation

Magnetic solid-phase extraction (m-SPE) is a promising sample preparation approach due to its convenience, speed, and simplicity. For the first time, a rapid and reliable m-SPE approach using magnetic multi-walled carbon nanotubes (m-MWCNTs) as the adsorbent was proposed for purification of type A trichothecenes including T-2 toxins (T2), HT-2 toxins (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO) in coix seed. The m-MWCNTs were synthesized by assembling the magnetic nanoparticles (Fe3O4) with MWCNTs by sonication through an aggregation wrap mechanism, and characterized by transmission electron microscope. Several key parameters affecting the performance of the procedure were extensively investigated including extraction solutions, desorption solvents, and m-MWCNT amounts. Under the optimal sample preparation conditions followed by analysis with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), high sensitivity (limit of quantification in the range of 0.3-1.5 μg kg(-1)), good linearity (R (2) > 0.99), satisfactory recovery (73.6-90.6 %), and acceptable precision (≤2.5 %) were obtained. The analytical performance of the developed method has also been successfully evaluated in real coix seed samples. Graphical Abstract Flow chart of determination of type A trichothecenes in coix seed by magnetic solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry.

Topics: Chromatography, High Pressure Liquid; Coix; Limit of Detection; Magnetics; Nanotubes, Carbon; Seeds; Solid Phase Extraction; T-2 Toxin; Tandem Mass Spectrometry; Trichothecenes

This paper reports a new method for the determination of T-2 and HT-2 toxins and their glucosylated derivatives in cereals, and some survey data aimed at obtaining more comprehensive information on the co-occurrence of T-2 and HT-2 toxins and their glucosylated derivatives in naturally contaminated cereal samples. For these purposes, barley samples originating from a Northern Italian area were analysed by LC-HRMS for the presence of T-2, HT-2 and relevant glucosyl derivatives. Quantitative analysis of T-2 and HT-2 glucosides was performed for the first time using a recently made available standard of T-2 glucoside. The glucosyl derivative of HT-2 was detected at levels up to 163 µg kg(-1) in 17 of the 18 analysed unprocessed barley grains, whereas the monoglucosyl derivative of T-2 toxin was detected in only a few samples and at low µg kg(-1) levels. The ratio between glucosylated toxins (sum of T-2 and HT-2 glucosides) and native toxins (sum of T-2 and HT-2) ranged from 2% to 283%. Moreover, taking advantage of the possibility of retrospective analysis of full-scan HRMS chromatograms, samples were also screened for the presence of other type-A trichothecenes, namely neosolaniol, diacetoxyscirpenol and their monoglucosyl derivatives, which were detected at trace levels. A subset of nine different samples was subjected to micro-maltation in order to carry out a preliminary investigation on the fate of T-2, HT-2 and relevant glucosides along the malting process. Mycotoxin reduction from cleaned barley to malt was observed at rates ranging from 4% to 87%.

Topics: Chromatography, Liquid; Edible Grain; Food Analysis; Glucosides; Hordeum; Humans; Limit of Detection; Mass Spectrometry; Reproducibility of Results; T-2 Toxin; 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

A Fusarium species with a micro morphology similar to F. poae and a metabolite profile resembling that of F. sporotrichioides has been identified. Like typical F. poae, the microconidia have a globose to pyriform shape, but the powdery appearance, especially on Czapek-Dox Iprodione Dichloran agar (CZID), less aerial mycelium and the lack of fruity odour on Potato Sucrose Agar (PSA) make it different from F. poae. The lack of macroconidia, polyphialides and chlamydospores differentiates it from F. sporotrichioides. All 18 isolates investigated, 15 Norwegian, two Austrian and one Dutch, produced T-2 toxin (25-400 micrograms/g) on PSA or Yeast Extract Sucrose agar (YES). In addition, neosolaniol, iso-neosolaniol, HT-2 toxin, 4- and 15-acetyl T-2 tetraol, T-2 triol and T-2 tetraol and 4,15-diacetoxyscirpenol were formed in variable amounts. Neither nivalenol, 4- or 15-acetylnivalenol or 4,15-diacetylnivalenol were detected in any of the cultures, while these toxins were produced at least in small amounts by all the 12 typical F. poae isolates studied. The question of whether this Fusarium should be classified as F. poae or F. sporotrichioides or a separate taxon should be addressed.

Topics: Edible Grain; Fusarium; Norway; Species Specificity; T-2 Toxin; Trichothecenes

Twenty-nine Fusarium isolates, representing three new taxa originated by Nirenberg from F. sambucinum Fuckel sensu lato, namely: F. sambucinum Fuckel sensu stricto, F. venenotum Nirenb., and F. torulosum (Berk. & Curt.) Nirenb., were tested for in vitro production of toxic secondary metabolites on autoclaved corn kernels. F. sambucinum sensu stricto was able to produce type A trichothecenes and enniatin B (EB). In particular, amongst the 14 isolates tested, 5 produced only diacetoxyscirpenol (DAS) (up to 700 micrograms/g); 1 produced only neosolaniol (NEOS) (250 micrograms/g); 2 produced T-2 toxin (T-2) + NEOS (up to 175 and 150 micrograms/g, respectively); 1 produced NEOS + DAS (300 and 100 micrograms/g, respectively); and 5 produced DAS + EB (up to 500 and 140 micrograms/g, respectively). All six isolates of F. venenotum were able to produce only DAS (up to 100 micrograms/g). F. torulosum produced no trichothecenes, but four out of nine tested isolates were able to produce EB (up to 140 micrograms/g). Zearalenones and type B trichothecenes were not found. The toxicity of the culture extracts towards Artemia salina L. was correlated in general with the occurrence of the above toxins, except for some F. torulosum strains. However, the lack of correlation between the amounts of toxins recovered and toxic activity observed in the Geotrichum candidum Link ex Pers. and A. salina assays suggested the presence of unknown toxic compounds.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Artemia; Depsipeptides; Fusarium; Geotrichum; Peptides; Species Specificity; T-2 Toxin; Trichothecenes; Zearalenone

This study compared the pathological and haematological effects of neosolaniol monoacetate in male Wistar rats with those of diacetoxyscirpenol, a highly toxic trichothecene mycotoxin. Both toxins caused statistically significant decreases in erythrocyte counts and increased the proportion of larger platelets compared to controls when dosed at 1 mg/kg body weight three times/wk for up to 5 wk. Lesions caused by treatment with either toxin at this dosage level were mild and were seen--mainly after 2-4 wk--in the actively dividing cells of the thymus, spleen, lymph nodes and bone marrow. Reduced severity or disappearance of the lesions was noted towards the end of the treatment period. The type and severity of the toxic effects of neosolaniol monoacetate appeared to be similar to those of diacetoxyscirpenol.

Topics: Animals; Erythrocyte Count; Fusarium; Male; Mycotoxins; Platelet Count; Rats; Sesquiterpenes; Trichothecenes