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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 -
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 -
Molecules (Basel, Switzerland) Nov 2022This study evaluated the ability of selected strains of , . , and . to inhibit mycelium growth and the biosynthesis of mycotoxins deoxynivalenol (DON), nivalenol (NIV),...
This study evaluated the ability of selected strains of , . , and . to inhibit mycelium growth and the biosynthesis of mycotoxins deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEN), α-(α-ZOL) and β-zearalenol (β-ZOL) by selected strains of and . . For this purpose, an in vitro experiment was carried out on solid substrates (PDA and rice). After 5 days of co-culture, it was found that all strains used in the experiment significantly inhibited the growth of mycelium. Qualitative assessment of pathogen-antagonist interactions showed that colonized 75% to 100% of the medium surface (depending on the species and strain of the antagonist and the pathogen) and was also able to grow over the mycelium of the pathogen and sporulate. The rate of inhibition of mycelium growth by ranged from approximately 24% to 66%. When and were co-cultured on rice, strains were found to inhibit DON biosynthesis by about 73% to 98%, NIV by about 87% to 100%, and ZEN by about 12% to 100%, depending on the pathogen and antagonist strain. A glycosylated form of DON was detected in the co-culture of . and whereas it was absent in cultures of the pathogen alone, thus suggesting that is able to glycosylate DON. The results also suggest that a strain of . is able to convert ZEN into its hydroxylated derivative, β-ZOL.
Topics: Fusarium; Trichoderma; Trichothecenes; Mycotoxins; Zearalenone; Oryza
PubMed: 36500242
DOI: 10.3390/molecules27238146 -
Toxins Nov 2022Zearalenone (ZON), zearalanone (ZAN) and their phase I metabolites: α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), α-zearalalanol (α-ZAL) and β-zearalalanol (β-ZAL)...
Zearalenone (ZON), zearalanone (ZAN) and their phase I metabolites: α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), α-zearalalanol (α-ZAL) and β-zearalalanol (β-ZAL) are compounds with estrogenic activity that are metabolized and distributed by the circulatory system in animals and can access the food chain through meat products from livestock. Furthermore, biomonitoring of zearalenones in biological matrices can provide useful information to directly assess mycotoxin exposure; therefore, their metabolites may be suitable biomarkers. The aim of this study was to determine the presence of ZON, ZAN and their metabolites in alternative biological matrices, such as liver, from three different animals: chicken, pig and lamb, in order to evaluate their exposure. A solid-liquid extraction procedure coupled to a GC-MS/MS analysis was performed. The results showed that 69% of the samples were contaminated with at least one mycotoxin or metabolite at varying levels. The highest value (max. 152.62 ng/g of β-ZOL) observed, and the most contaminated livers (42%), were the chicken liver samples. However, pig liver samples presented a high incidence of ZAN (33%) and lamb liver samples presented a high incidence of α-ZOL (40%). The values indicate that there is exposure to these mycotoxins and, although the values are low (ranged to 0.11-152.6 ng/g for α-ZOL and β-ZOL, respectively), analysis and continuous monitoring are necessary to avoid exceeding the regulatory limits and to control the presence of these mycotoxins in order to protect animal and human health.
Topics: Humans; Swine; Sheep; Animals; Zearalenone; Chickens; Tandem Mass Spectrometry; Mycotoxins; Liver
PubMed: 36422956
DOI: 10.3390/toxins14110782 -
Toxics Nov 2022As one of the most prevalent estrogenic mycotoxins in cereals and animal feed, zearalenone (ZEN) can cause serious reproductive disorders. ZEN control in food and feed...
As one of the most prevalent estrogenic mycotoxins in cereals and animal feed, zearalenone (ZEN) can cause serious reproductive disorders. ZEN control in food and feed commodities has been an imperative area of research. In this study, 87 lactic acid bacteria (LAB) were isolated from pickles and their ZEN (5 mg/L) removal abilities ranged from 0% to 68.4%. Then, five strains with potent ZEN removal ability (>50%) were identified: Lactobacillus plantarum 22, L. plantarum 37, L. plantarum 47, L. paracasei 85, and L. buchneri 93. Under optimization conditions (48 h, pH 4.0, 37 °C, and 5 mg/L), the highest ZEN removal abilities of L. paracasei 85 and L. buchneri 93 reached 77.7% and 72.8%, respectively. Moreover, the two lactic acid bacteria decreased the toxicity of ZEN, because the levels of β-zearalenol (β-ZOL) transformed from ZEN were more than two-fold higher than α-zearalenol (α-ZOL). Additionally, cell free supernatant and pellet biotransformation of ZEN to α-ZOL and β-ZOL in LAB were detected for the first time. Furthermore, chemical and enzymatical treatments combined with Fourier-transform infrared spectroscopy analysis indicated that exopolysaccharides, proteins, and lipids on the cell wall could bond to ZEN through hydrophobic interactions. Scanning electron microscopy indicated that cell structure damage occurred during the ZEN clearance to L. buchneri 93, but it did not with L. paracasei 85. In addition, various organic acids, alcohols, and esters of the two LAB participated in ZEN removal. Hence, L. paracasei 85 and L. buchneri 93 can be considered as potential detoxification agents for ZEN removal for food and feedstuff.
PubMed: 36355971
DOI: 10.3390/toxics10110680 -
Toxins Oct 2022The aim of this study was to explore the effect of zearalenone (ZEA) exposure on uterine development in weaned gilts by quantitative proteome analysis with tandem mass...
The aim of this study was to explore the effect of zearalenone (ZEA) exposure on uterine development in weaned gilts by quantitative proteome analysis with tandem mass spectrometry tags (TMT). A total of 16 healthy weaned gilts were randomly divided into control (basal diet) and ZEA3.0 treatments groups (basal diet supplemented with 3.0 mg/kg ZEA). Results showed that vulva size and uterine development index were increased (p < 0.05), whereas serum follicle stimulation hormone, luteinizing hormone and gonadotropin-releasing hormone were decreased in gilts fed the ZEA diet (p < 0.05). ZEA, α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) were detected in the uteri of gilts fed a 3.0 mg/kg ZEA diet (p < 0.05). The relative protein expression levels of creatine kinase M-type (CKM), atriopeptidase (MME) and myeloperoxidase (MPO) were up-regulated (p < 0.05), whereas aldehyde dehydrogenase 1 family member (ALDH1A2), secretogranin-1 (CHGB) and SURP and G-patch domain containing 1 (SUGP1) were down-regulated (p < 0.05) in the ZEA3.0 group by western blot, which indicated that the proteomics data were dependable. In addition, the functions of differentially expressed proteins (DEPs) mainly involved the cellular process, biological regulation and metabolic process in the biological process category. Some important signaling pathways were changed in the ZEA3.0 group, such as extracellular matrix (ECM)-receptor interaction, focal adhesion and the phosphoinositide 3-kinase−protein kinase B (PI3K-AKT) signaling pathway (p < 0.01). This study sheds new light on the molecular mechanism of ZEA in the uterine development of gilts.
Topics: Animals; Female; Aldehyde Dehydrogenase 1 Family; Chromogranins; Creatine Kinase; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Neprilysin; Peroxidase; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proteome; Proteomics; Proto-Oncogene Proteins c-akt; Sus scrofa; Swine; Zearalenone
PubMed: 36287961
DOI: 10.3390/toxins14100692 -
Foods (Basel, Switzerland) Sep 2022Zearalenone (ZEN) and its derivatives pose a serious threat to global food quality and animal health. The use of enzymes to degrade mycotoxins has become a popular...
Zearalenone (ZEN) and its derivatives pose a serious threat to global food quality and animal health. The use of enzymes to degrade mycotoxins has become a popular method to counter this threat. In this study, Aspergillus niger ZEN-S-FS10 extracellular enzyme solution with ZEN-degrading effect was separated and purified to prepare the biological enzyme, FSZ, that can degrade ZEN. The degradation rate of FSZ to ZEN was 75−80% (pH = 7.0, 28 °C). FSZ can function in a temperature range of 28−38 °C and pH range of 2.0−7.0 and can also degrade ZEN derivatives (α-ZAL, β-ZOL, and ZAN). According to the enzyme kinetics fitting, ZEN has a high degradation rate. FSZ can degrade ZEN in real samples of corn flour. FSZ can be obtained stably and repeatedly from the original strain. One ZEN degradation product was isolated: FSZ−P(C18H26O4), with a relative molecular weight of 306.18 g/mol. Amino-acid-sequencing analysis revealed that FSZ is a novel enzyme (homology < 10%). According to the results of molecular docking, ZEN and ZAN can utilize their end-terminal carbonyl groups to bind FSZ residues PHE307, THR55, and GLU129 for a high-degradation rate. However, α-ZAL and β-ZOL instead contain hydroxyl groups that would prevent binding to GLU129; thus, the degradation rate is low for these derivatives.
PubMed: 36141036
DOI: 10.3390/foods11182908 -
Food Chemistry Jan 2023The aim of this manuscript was to validate and apply an analytical methodology for the simultaneous determination of 34 mycotoxins in cocoa. The extraction method used...
The aim of this manuscript was to validate and apply an analytical methodology for the simultaneous determination of 34 mycotoxins in cocoa. The extraction method used in the tests was a liquid-liquid partition by NaCl addition with a freezing step followed by quantification using LC-MS/MS. The results were discussed based on national and international directives for food contaminants. The recoveries and precision were adequate, except for the mycotoxins ionized with the ammonium adduct (NH), E-cristinine and β-ZOL. This result directly influenced the measurement uncertainty of these mycotoxins, because the precision and the correction factor of the recovery were the factors with the greatest impact on the uncertainty of the method. The evaluation of the matrix effect showed considerable signal suppression for 53 % of the evaluated mycotoxins. Nevertheless, the mycotoxins exhibited relatively low quantification limits, with values between 1 and 75 μg kg. The validated methodology was applied to 15 cocoa samples collected in warehouses in Brazil. Positive results were found for all the evaluated samples, in which nine toxins were detected out of the 34 investigated.
Topics: Cacao; Chromatography, High Pressure Liquid; Chromatography, Liquid; Mycotoxins; Tandem Mass Spectrometry; Uncertainty
PubMed: 36027808
DOI: 10.1016/j.foodchem.2022.133902 -
Toxins Nov 2021The purpose of this research was to investigate the toxicity of zearalenone (ZEN) on the growth performance, genital organs, serum hormones, biomarkers, and...
The purpose of this research was to investigate the toxicity of zearalenone (ZEN) on the growth performance, genital organs, serum hormones, biomarkers, and histopathological changes of female gilts and to evaluate the efficacy of ZJ-2019-1 in alleviating ZEN toxicosis in gilts. Twenty-four female gilts were randomly allocated to four groups with six replicates per group and one gilt per replicate, fed on four feeds prepared previously, which were basic diet (control group, C group), ZEN diet (Z group), Zlb diet (Zlb group) containing B. subtilis ZJ-2019-1 in liquid form, and Zdb diet (Zdb group) containing ZJ-2019-1 in dehydrated form. The results showed that the vulva size and relative weight of reproductive organs had no significant difference in the control group, Zlb group, and Zdb group, but were significantly lower than in the Z group ( < 0.05); the relative weight of the liver was lower in the C group, Zlb group, and Zbd group than in the Z group (0.05 < < 0.1). The concentration of serum glutamate dehydrogenase (GLDH) was lower, but follicle-stimulating hormone (FSH) was higher in the Z group, Zlb group, and Zdb group than in the Z group (0.05 < < 0.1). Additionally, serum luteinizing hormone (LH) concentration had no significant difference in the C group, Zlb group, and Zdb group but was significantly lower than in the Z group ( < 0.05); estradiol (E2) was significantly lower in the Zlb group and Zdb group than that in C group, but significantly higher than that in Z group ( < 0.05); PRL was significantly higher in the Zlb group and Zdb group than in the C group, but was significantly lower than in Z group ( < 0.05). ZEN and its reduced metabolites were measured in biological samples after enzymatic hydrolysis of the conjugated forms. The concentration of serum ZEN and its metabolite, α-zeralenol (α-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group ( < 0.05); urine ZEN and its metabolites, α-ZOL and β-zeralenol (β-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group ( < 0.05). Cell damages were observed in the liver, uterus, and ovary of gilts in the Z group and alleviated in Zlb and Zdb groups, but the loss of oocytes was irreversible in the ovary. The ZEN-contaminated diet caused serious changes in female hormones and brought harm to the livers and reproductive organs, but ZJ-2019-1 could naturally remove the ZEN significantly, which ameliorated the reproductive impairment in gilts caused by ZEN. The addition of ZJ-2019-1 to ZEN-contaminated feeds could ameliorate the toxic effects effectively, regardless of liquid or dry culture. Therefore, the ZJ-2019-1 strain has great potential industrial applications.
Topics: Animals; Bacillus subtilis; Estrogens, Non-Steroidal; Female; Mycotoxins; Sus scrofa; Zearalenone
PubMed: 34822572
DOI: 10.3390/toxins13110788 -
International Journal of Analytical... 2021This study aimed to explore the zearalenone (ZEN) immunogen synthesis method, immunogenicity, and antibody characteristics and to lay a foundation for the establishment...
BACKGROUND
This study aimed to explore the zearalenone (ZEN) immunogen synthesis method, immunogenicity, and antibody characteristics and to lay a foundation for the establishment of immunoassay methods for ZEN single residue and ZEN and its analogs total residue.
METHODS
Based on the molecular structure and active sites of ZEN, oxime active ester (OAE), condensation mixed anhydride (CMA), formaldehyde (FA), and 1,4-butanediol diglycidyl ether method (BDE) were designed and used for immunogen (ZEN-BSA) synthesis. The immunogens were identified by infrared (IR) and ultraviolet (UV) spectra and gel electrophoresis (SDS-PAGE) and were then used to immunize Balb/c mice to prepare ZEN polyclonal antibody (ZEN pAb). The titers and sensitivity of the ZEN pAb were determined by indirect noncompetitive ELISA (inELISA) and indirect competitive ELISA (icELISA), respectively, and its specificity was assessed by the cross-reaction test (CR).
RESULTS
ZEN-BSA was successfully synthesized, and the molecular binding ratios of ZEN to BSA were 17.2 : 1 (OAE), 14.6 : 1 (CMA), 9.7 : 1 (FA), and 8.3 : 1 (BDE), respectively. The highest inELISA titers of ZEN pAb of each group were 1 : (6.4 × 10) (OAE), 1 : (3.2 × 10) (CMA), 1 : (1.6 × 10) (FA), and 1 : (1.6 × 10) (BDE), respectively. The 50% inhibition concentrations (IC50) for ZEN by icELISA of each group were 11.67 g/L (OAE), 16.29 g/L (CMA), 20.92 g/L (FA) and 24.36 g/L (BDE), respectively. ZEN pAb from the mice immunized with ZEN-BSA (OAE) and ZEN-BSA (CMA) had class broad specificity to ZEN and its analogs. The CRs of ZEN pAb with -ZAL, -ZAL, -ZOL, -ZOL, and ZON were 36.53%, 16.98%, 64.33%, 20.16%, and 10.66%, respectively. ZEN pAb from the mice immunized with ZEN-BSA (FA) and ZEN-BSA (BDE) had high specificity for ZEN. The CRs of ZEN pAb with its analogs were all less than 1.0%.
CONCLUSION
This study demonstrated that the preparation of the class broad-specificity antibodies of ZEN and its analogs can be achieved by immunizing animals with the immunogen ZEN-BSA prepared by the OAE method, while the preparation of highly specific antibodies can be achieved by immunizing animals with the immunogen ZEN-BSA prepared by the FA method. These findings lay the material and technical foundation for immunoassay of ZEN single residue and ZEN and its analogs total residue.
PubMed: 34349801
DOI: 10.1155/2021/7109383