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Molecules (Basel, Switzerland) Nov 2017Zearalenone (ZEN) is a mycotoxin produced by fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN...
Zearalenone (ZEN) is a mycotoxin produced by fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN is a fluorescent mycotoxin, although molecular interactions and microenvironmental changes significantly modify its spectral properties. During biotransformation, ZEN is converted into α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL), the toxic metabolites of ZEN, which mimick the effect of estrogen. Cyclodextrins (CDs) are host molecules, and have been studied extensively; they can form stable complexes with several mycotoxins, including ZEN. However, information is limited regarding the interactions of CDs with ZOLs. Therefore, we studied the interactions of α- and β-ZOLs with native and six chemically modified β-CDs by fluorescence spectroscopy. Fluorescence enhancement during complex formation, as well as binding constants, were determined. To understand ZOL-CD interactions better, molecular modeling studies were also carried out. Both mycotoxin derivatives formed the most stable complexes with methylated and sulfobutylated CD-derivatives; however, the CD complexes of α-ZOL were significantly stronger than those of β-ZOL. The data presented here indicate which of the chemically modified β-CDs appear more suitable as fluorescence enhancers or as potential mycotoxin binders.
Topics: Animals; Humans; Models, Molecular; Molecular Structure; Protein Conformation; Protein Stability; Spectrometry, Fluorescence; Zeranol; beta-Cyclodextrins
PubMed: 29113131
DOI: 10.3390/molecules22111910 -
Theranostics 2023Prolonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the inflammation response, we designed a rapid drug...
Prolonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the inflammation response, we designed a rapid drug screening paradigm in larval zebrafish followed by testing of hit compounds in a mouse spinal cord injury model. We used reduced linked green fluorescent protein (GFP) reporter gene expression as a read-out for reduced inflammation in a screen of 1081 compounds in larval zebrafish. Hit drugs were tested in a moderate contusion model in mice for cytokine regulation, and improved tissue preservation and locomotor recovery. Three compounds robustly reduced expression in zebrafish. Cimetidine, an over-the-counter H2 receptor antagonist, also reduced the number of pro-inflammatory neutrophils and rescued recovery after injury in a zebrafish mutant with prolonged inflammation. Cimetidine action on expression levels was abolished by somatic mutation of H2 receptor , suggesting specific action. In mice, systemic treatment with Cimetidine led to significantly improved recovery of locomotor behavior as compared to controls, accompanied by decreased neuronal tissue loss and a shift towards a pro-regenerative profile of cytokine gene expression. Our screen revealed H2 receptor signaling as a promising target for future therapeutic interventions in spinal cord injury. This work highlights the usefulness of the zebrafish model for rapid screening of drug libraries to identify therapeutics to treat mammalian spinal cord injury.
Topics: Mice; Animals; Zebrafish; Cimetidine; Larva; Drug Evaluation, Preclinical; Spinal Cord Injuries; Inflammation; Cytokines; Mammals
PubMed: 37215570
DOI: 10.7150/thno.81332 -
Green Chemistry : An International... May 2021As an alternative to classical synthetic approaches for the production of betazole drug, a one-pot biocatalytic system for this pharmaceutical molecule from its alcohol...
As an alternative to classical synthetic approaches for the production of betazole drug, a one-pot biocatalytic system for this pharmaceutical molecule from its alcohol precursor has been developed. An ω-transaminase, an alcohol dehydrogenase and a water-forming NADH oxidase for cofactor recycling have been combined to catalyse this reaction, yielding 75% molar conversion in batch reactions with soluble enzymes. This multienzyme system was then co-immobilised through a newly established protocol for sequential functionalization of a methacrylate-based porous carrier to enable tailored immobilisation chemistries for each enzyme. This pluri-catalytic system has been set up in a continuous flow packed-bed reactor, generating a space-time yield of up to 2.59 g L h with 15 min residence and a constant supply of oxygen for cofactor recycling through a segmented air-liquid flow. The addition of an in-line catch-and-release column afforded >80% product recovery.
PubMed: 34220333
DOI: 10.1039/d1gc01095f -
Gut Feb 1974Basal, as well as betazole-stimulated gastric acid secretion in man is reduced after the intravenous administration of bromazepam. In subjects staying awake, this...
Basal, as well as betazole-stimulated gastric acid secretion in man is reduced after the intravenous administration of bromazepam. In subjects staying awake, this reduction is limited to the first two 15-minute periods. The reduction is highly significant in subjects who fall asleep after receiving the drug. Natural sleep causes the same depression. The low level of acid secretion is maintained until the subjects are awakened when there is a sharp and highly significant rise. Acid secretion in subjects who fall asleep after the simultaneous administration of betazole and bromazepam is significantly higher than after the administration of bromazepam alone. Sleep causes a much greater depression of basal and betazole-stimulated acid secretion than does the benzodiazepine itself. Acid secretion was measured by continuous intragastric titration and a pH-sensitive endoradiosonde.
Topics: Adult; Benzodiazepinones; Ethylamines; Female; Gastric Juice; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Injections, Subcutaneous; Male; Pyrazoles; Pyridines; Sleep; Telemetry
PubMed: 4820635
DOI: 10.1136/gut.15.2.116 -
Toxins Jan 2024Zearalenone (ZEN) is a mycotoxin produced by various Fusarium strains, that is present in food and feed raw materials worldwide, causing toxicity effects in animals and...
Zearalenone (ZEN) is a mycotoxin produced by various Fusarium strains, that is present in food and feed raw materials worldwide, causing toxicity effects in animals and humans. This research aimed to explore the toxicokinetics of ZEN on female Dezhou donkeys following a single oral exposure dosage of 2 mg/kg BW (body weight). The sample collection of donkeys plasma was carried out at 0, 5, 10, 15, 20, 30, 45, 60, 90 min, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 6 h, 9 h, 12 h, 24 h, 48 h, 72 h, 96 h and 120 h via intravenous catheter, and fecal and urinary samples were severally collected at 0 h and every 6 h until 120 h. The concentrations of ZEN, α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), zearalanone (ZAN) in plasma, urine, and feces were detected by UPLC-MS/MS. Only ZEN was detected in plasma, and the maximum was 15.34 ± 5.12 µg/L occurred at 0.48 h after gavage. The total plasma clearance (Cl) of ZEN was 95.20 ± 8.01 L·kg·BW·h. In addition, the volume of distribution (Vd) was up to 216.17 ± 58.71 L/kg. The percentage of total ZEN (ZEN plus the main metabolites) excretion in feces and urine was 2.49% and 2.10%, respectively. In summary, ZEN was fast absorbed and relatively slowly excreted in female donkeys during 120 h after a single gavage, indicating a trend of wider tissue distribution and longer tissue persistence.
Topics: Female; Animals; Humans; Zearalenone; Toxicokinetics; Chromatography, Liquid; Tandem Mass Spectrometry; Administration, Oral; Zeranol
PubMed: 38251267
DOI: 10.3390/toxins16010051 -
Toxins Jun 2019The determination of mycotoxin and metabolite concentrations in human and animal urine is currently used for risk assessment and mycotoxin intake measurement. In this...
The determination of mycotoxin and metabolite concentrations in human and animal urine is currently used for risk assessment and mycotoxin intake measurement. In this study, pig urine ( = 195) was collected at slaughterhouses in 2012 by the Swedish National Food Agency in three counties representing East, South and West regions of Sweden. Urinary concentrations of four mycotoxins, (deoxynivalenol (DON), zearalenone (ZEA), fumonisin B (FB), and ochratoxin A (OTA)), and four key metabolites, (deepoxy-deoxynivalenol (DOM-1), aflatoxin M (AFM, biomarker of AFB), α-zearalenol (α-ZOL), and β-zearalenol (β-ZOL)) were identified and measured by UPLC-MS/MS. Statistically significant regional differences were detected for both total DON (DON + DOM-1) and total ZEA (ZEA + α-ZOL + β-ZOL) concentrations in pig urine from the three regions. These regional differences were in good agreement with the occurrence of mycotoxins (DON + ZEA) in cereal grains harvested in 2011 in Sweden. There were no statistically significant differences in FB, AFM and OTA urinary concentrations in pigs from the three regions. The overall incidence of positive samples was high for total ZEA (99-100%), total DON (96-100%) and OTA (85-95%), medium for FB (30-61%) and low for AFM (0-13%) in the three regions. Urinary mycotoxin biomarker concentrations were used to estimate mycotoxin intake and the level of mycotoxins in feeds consumed by the monitored pigs. The back-calculated levels of mycotoxins in feeds were low with the exception of seven samples that were higher the European limits.
Topics: Animal Feed; Animals; Biological Monitoring; Biomarkers; Food Contamination; Geography; Mycotoxins; Sweden; Swine
PubMed: 31262000
DOI: 10.3390/toxins11070378 -
Reproductive Biology and Endocrinology... Nov 2006The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in...
BACKGROUND
The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs) from the ovaries of cycling mares.
METHODS
The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 x 10-7 to 0.1 microM). The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry.
RESULTS
An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 x 10-3 and 1 x 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations.
CONCLUSION
The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare.
Topics: Animal Feed; Animals; Apoptosis; Cell Division; Cells, Cultured; DNA; Estrogens, Non-Steroidal; Female; Flow Cytometry; Follicular Atresia; Food Contamination; Granulosa Cells; Horses; Zearalenone; Zeranol
PubMed: 17137489
DOI: 10.1186/1477-7827-4-62 -
Toxins Feb 2011Zearalenone (ZON) is a mycotoxin with estrogenic activity, produced by members of Fusarium species, and is found worldwide in a number of cereal crops. It is known to...
Zearalenone (ZON) is a mycotoxin with estrogenic activity, produced by members of Fusarium species, and is found worldwide in a number of cereal crops. It is known to have four active metabolites (α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), α-zearalanol (α-ZAL), and β-zearalanol (β-ZAL)). A highly sensitive analytical method using liquid chromatography/tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) has been established and validated in order to analyze ZON and its metabolites in beer and malt samples. The metabolism of ZON in the course of beer fermentation was further characterized using the artificially contaminated wort by this established method. In the fermented sample, 85.9% of ZON was converted to β-ZOL, which has lower estrogenic activity than that of ZON. These findings indicate that the health risk to humans due to ZON in beer is reduced during the fermentation process.
Topics: Beer; Estrogens, Non-Steroidal; Fermentation; Food Contamination; Saccharomyces; Zearalenone
PubMed: 22069701
DOI: 10.3390/toxins3020134 -
Food and Chemical Toxicology : An... May 2008Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites... (Comparative Study)
Comparative Study
Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites identified in vitro and in vivo: alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). The efficiency to produce alpha-reduced metabolites appears of particular interest in risk assessment as alpha-reduced metabolites constitute activated forms whereas beta-reduced metabolites are less oestrogenic than ZEA. In this study ZEA activation was compared in avian food species. ZEA and its reduced metabolites were quantified in subcellular fractions of six avian species and rat livers. The alpha-ZOL/beta-ZOL ratio in rats was 19. The various avian food species cannot be considered to be equivalent in terms of ZEA reduction (P<0.001). Quails represented high "beta reducers", with alpha-ZOL/beta-ZOL ratio less than two. Weak "beta reducers" included on one part ducks and chickens showing alpha-ZOL/beta-ZOL ratio greater than 3 and up to 5.6 and on a second part geese, showing a lower production of alpha-ZOL than other poultry. Comparisons of enzyme kinetics in ducks and in quails show that these variations can be explained by the action of various isoforms of dehydrogenases. These results are relevant to food safety, in the context of frequently inevitable contamination of animal feed.
Topics: Animals; Biotransformation; Birds; Chickens; Chromatography, High Pressure Liquid; Ducks; Estrogens, Non-Steroidal; Geese; Indicators and Reagents; Kinetics; Male; Meat; Oxidoreductases; Poultry; Quail; Rats; Rats, Sprague-Dawley; Species Specificity; Subcellular Fractions; Zearalenone
PubMed: 18221829
DOI: 10.1016/j.fct.2007.12.008 -
Toxins Nov 2019Consumption of fruit juice is becoming trendy for consumers seeking freshness and high vitamin and low caloric intake. Mycotoxigenic moulds may infect fruits during crop...
Consumption of fruit juice is becoming trendy for consumers seeking freshness and high vitamin and low caloric intake. Mycotoxigenic moulds may infect fruits during crop growth, harvest, and storage leading to mycotoxin production. Many mycotoxins are resistant to food processing, which make their presence in the final juice product very likely expected. In this way, the presence of 30 mycotoxins including aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), alternariol (AOH), alternariol monomethyl ether (AME), Ochratoxin A (OTA), fumonisin B1 (FB1), fumonisin B2 (FB2), enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), beauvericin (BEA), sterigmatocystin (STG), zearalenone (ZEA), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl-deoxynivalenol (15-ADON), diacetoxyscirpenol (DAS), nivalenol (NIV), fusarenon-X (FUS-X), neosolaniol (NEO), patulin (PAT), T-2 toxin and HT-2 toxin was evaluated in 80 juice samples collected from Valencia retail Market. An efficient Dispersive Liquid-Liquid Microextraction method (DLLME) was carried out before their trace level determination by chromatographic techniques coupled to tandem mass spectrometry. The results obtained revealed the presence of nine mycotoxins namely AOH, AME, PAT, OTA, AFB1, AFB2, AFG2, β-ZAL, and HT2 in the analyzed samples, with incidences ranging from 3 to 29% and mean contents between 0.14 and 59.52 µg/L. Considerable percentages of TDIs were reached by children when 200 mL was considered as daily fruit juice intake.
Topics: Adult; Child; Citrus; Dietary Exposure; Female; Food Contamination; Fruit and Vegetable Juices; Glycogen Storage Disease Type III; Humans; Liquid Phase Microextraction; Male; Malus; Mycotoxins; Reproducibility of Results; Risk Assessment; Tandem Mass Spectrometry
PubMed: 31766649
DOI: 10.3390/toxins11120684