RESUMO
Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17ß-estradiol (E2), they interact with estrogen receptors α/ß earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (nâ¯=â¯297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.
Assuntos
Sangue Fetal , Zearalenona , Humanos , Feminino , Sangue Fetal/química , Gravidez , Zearalenona/urina , Zearalenona/sangue , Adulto , Masculino , Hormônios Esteroides Gonadais/sangue , Exposição Materna , Estudos de Coortes , Zeranol/análogos & derivados , Zeranol/urina , Estradiol/sangue , Adulto Jovem , Placenta/químicaRESUMO
DON and ZEN residues in the blood and urine of dairy cows can be used to predict the outer exposure to DON and ZEN expressed per kilogram diet for a risk evaluation based on comparisons to critical dietary concentrations. This method was used to evaluate the exposure of dairy cows from 12 farms located in Brandenburg, Germany, fed rations with unknown DON and ZEN concentrations (N = 244). The corresponding diet concentrations predicted by different methods from analyzed blood and urine samples varied significantly amongst farms from 0 to 1.6 mg/kg for DON and 0 to 3.0 mg/kg for ZEN at a reference dry matter content of 88% but independently of lactational state (post-partum vs. early lactation). This significant variation was noticed below the critical dietary DON concentration of 5 mg/kg, while the ZEN concentration in one farm exceeded the critical ZEN level of 0.5 mg/kg markedly. Predicted DON concentrations of rations increased with the proportion of maize silage, while the high ZEN concentration found in one farm was most likely related to a higher proportion of sugar beet pulp supposedly highly contaminated by ZEN. Exceeding the critical dietary ZEN concentration and significant variations in DON contents below the critical level was not related to performance, reproductive performance, and health-related traits of cows. For a more consistent evaluation of possible associations between the inner exposure of cows to DON and ZEN, more frequent longitudinal observations of both mycotoxin residue levels and performance and health traits are required.
Assuntos
Tricotecenos , Zearalenona , Bovinos , Animais , Tricotecenos/urina , Tricotecenos/sangue , Tricotecenos/análise , Zearalenona/análise , Zearalenona/urina , Zearalenona/sangue , Medição de Risco , Feminino , Alemanha , Ração Animal/análise , Dieta/veterinária , Indústria de Laticínios , Urina/químicaRESUMO
This study explored and investigated how zearalenone (ZEA) affects the morphology of small intestine and the distribution and expression of ghrelin and proliferating cell nuclear antigen (PCNA) in the small intestine of weaned gilts. A total of 20 weaned gilts (42-day-old, D × L × Y, weighing 12.84 ± 0.26 kg) were divided into the control and ZEA groups (ZEA at 1.04 mg/kg in diet) in a 35-d study. Histological observations of the small intestines revealed that villus injuries of the duodenum, jejunum and ileum, such as atrophy, retardation and branching dysfunction, were observed in the ZEA treatment. The villi branch of the ileum in the ZEA group was obviously decreased compared to that of the ileum, jejunum and duodenum, and the number of lymphoid nodules of the ileum was increased. Additionally, the effect of ZEA (1.04 mg/kg) was decreased by the immunoreactivity and distribution of ghrelin and PCNA in the duodenal and jejunal mucosal epithelial cells. Interestingly, ZEA increased the immunoreactivity of ghrelin in the ileal mucosal epithelial cells and decreased the immunoreactivity expression of PCNA in the gland epithelium of the small intestine. In conclusion, ZEA (1.04 mg/kg) had adverse effects on the development and the absorptive capacity of the villi of the intestines; yet, the small intestine could resist or ameliorate the adverse effects of ZEA by changing the autocrine of ghrelin in intestinal epithelial cells.
Assuntos
Grelina/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Zearalenona/toxicidade , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/genética , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Intestino Delgado/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/genética , Sus scrofa , Zearalenona/sangueRESUMO
Mycotoxin contaminated feed has been associated with colic of horses caused by intestinal disorders. Whether such disease conditions alter the intestinal toxin metabolism and transfer across a compromised mucosal barrier is unknown. A screening approach was used to relate blood residue levels of DON, ZEN and their metabolites to the status of the horses (sick vs. healthy). A total of 55 clinically healthy horses from 6 different farms with varying feeding background served as control for sick horses (N = 102) hospitalized due to colic. ZEN, alpha-zearalenol (ZEL), beta-ZEL and DON were detectable in peripheral blood as indicators for the inner exposure with significant farm effects for alpha- and beta-ZEL. However, the levels in sick horses were similar to all farms. Moreover, the proportion of beta-ZEL of all detected ZEN metabolites as an indicator for the degree of metabolism of ZEN was not different for sick horses but differed amongst the control farms. Although the incidence of DON in blood was generally low and not significantly different amongst healthy and sick horses, the positive samples were nearly exclusively found in sick horses suggesting either a higher toxin transfer, an association of DON with the development of colic or a different feeding background.
Assuntos
Cólica/induzido quimicamente , Tricotecenos/sangue , Tricotecenos/metabolismo , Tricotecenos/toxicidade , Zearalenona/sangue , Zearalenona/metabolismo , Zearalenona/toxicidade , Ração Animal/análise , Ração Animal/microbiologia , Animais , Análise Química do Sangue , Cavalos , Micotoxinas/sangue , Micotoxinas/metabolismo , Micotoxinas/toxicidadeRESUMO
Zearalenone (ZEN) and its metabolites, alpha-zearalenol (α-ZEL) and beta-zearalenol (ß-ZEL), are ubiquitous in plant materials used as feed components in dairy cattle diets. The aim of this study was to confirm the occurrence of ZEN and its selected metabolites in blood samples collected from different sites in the hepatic portal system (posthepatic-external jugular vein EJV; prehepatic-abdominal subcutaneous vein ASV and median caudal vein MCV) of dairy cows diagnosed with mastitis, ovarian cysts and pyometra. The presence of mycotoxins in the blood plasma was determined with the use of combined separation methods involving immunoaffinity columns, a liquid chromatography system and a mass spectrometry system. The parent compound was detected in all samples collected from diseased cows, whereas α-ZEL and ß-ZEL were not identified in any samples, or their concentrations were below the limit of detection (LOD). Zearalenone levels were highest in cows with pyometra, where the percentage share of average ZEN concentrations reached 44%. Blood sampling sites were arranged in the following ascending order based on ZEN concentrations: EJV (10.53 pg/mL, 44.07% of the samples collected from this site), ASV (14.20 pg/mL, 49.59% of the samples) and MCV (26.67 pg/mL, 67.35% of the samples). The results of the study indicate that blood samples for toxicological analyses should be collected from the MCV (prehepatic vessel) of clinically healthy cows and/or cows with subclinical ZEN mycotoxicosis. This sampling site increases the probability of correct diagnosis of subclinical ZEN mycotoxicosis.
Assuntos
Bovinos/sangue , Mastite Bovina/sangue , Micotoxicose/sangue , Cistos Ovarianos/sangue , Piometra/sangue , Zearalenona/sangue , Ração Animal , Animais , Monitoramento Biológico , Dieta/veterinária , Feminino , Contaminação de Alimentos , Micotoxicose/veterinária , Cistos Ovarianos/veterinária , Piometra/veterináriaRESUMO
Juveniles are considered as one of the most vulnerable population groups concerning mycotoxins and their modified forms. The weaning stage is a particularly vulnerable period in the life of mammals, reflected in intestinal and immune dysfunction. The current study investigated the toxicokinetic (TK) characteristics of zearalenone (ZEN), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S) in weaned (4-week-old) piglets, by means of oral and intravenous administration of equimolar doses, i.e., 331, 500, and 415 µg/kg bodyweight, respectively. Plasma and urine were sampled pre- and post-administration and were quantitatively analyzed for ZEN, ZEN14G, ZEN14S, and in vivo metabolites by liquid chromatography-high-resolution mass spectrometry. Tailor-made TK models were elaborated to process data. A statistical comparison of the results was performed with TK data obtained in a previously reported study in pigs of 8 weeks of age. Additionally, porcine plasma protein binding was determined to support TK findings. The TK results for ZEN, ZEN14G, and ZEN14S, obtained in 4- and 8-week-old pigs, revealed significant age-related differences, based on differences in intestinal permeability, body fat content, gastrointestinal transit time, and biotransformation, with a special emphasis on an increased absorbed fraction of ZEN14G, i.e., 94 vs 61% in 4- compared to 8-week-old pigs. Since the growing pig has been reported to be a suitable pediatric animal model for humans concerning TK processes, these results may contribute to refine the risk assessment concerning modified ZEN forms in juvenile animals and humans.
Assuntos
Glucosídeos/farmacocinética , Suínos/sangue , Suínos/urina , Zearalenona/análogos & derivados , Zearalenona/farmacocinética , Fatores Etários , Animais , Feminino , Glucosídeos/sangue , Glucosídeos/toxicidade , Glucosídeos/urina , Masculino , Sulfatos/sangue , Sulfatos/toxicidade , Sulfatos/urina , Suínos/crescimento & desenvolvimento , Toxicocinética , Zearalenona/sangue , Zearalenona/toxicidade , Zearalenona/urinaRESUMO
Colorectal cancer (CRC) is one of the most common and lethal types of cancer worldwide. The developing of this disease includes many factors such as genetic, socioeconomic, environmental, and lifestyle factors, and nutrition habits. The aim of the study is the determination of zearalenone and its metabolite level in the biological samples of participants at risk of CRC, in relation to the nutrition data and information on the quality of life dependent on health. In the cohort clinical trial, 150 participants aged between 50 and 65 will be studied. The participants will be assigned into two groups depending on the colonoscopy result. Participants will be tested at dietary intake, quality of life, sleep time and quality, stress level as well as biochemical parameters of the blood. Moreover, in the biological samples, concentration of zearalenone and its metabolites (α-zearalenol and ß-zearalenol) as well as the characteristics of gastrointestinal bacterial will be determined, and the end of the trial for both groups and their results will be compared. Taking into account the possible effect of mycotoxins and nutrition habits on the development of cancer, the results obtained may allow the formulation of new nutritional recommendations and reduce the development and occurrence of CRC.
Assuntos
Neoplasias Colorretais/sangue , Dieta , Zearalenona/sangue , Idoso , Estudos de Coortes , Fezes/química , Feminino , Contaminação de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Qualidade de Vida , Projetos de Pesquisa , Fatores de RiscoRESUMO
The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52⯱â¯9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (pâ¯=â¯0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480â¯g/d) compared those with lowest (<115â¯g/d) meat consumption had higher conjugated serum ZEA metabolite concentrations (pâ¯<â¯0.05). Intakes of other food groups (i.e., dairy, cereal, etc.) were not associated with ZEA metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations.
Assuntos
Índice de Massa Corporal , Ingestão de Energia , Estrogênios não Esteroides/sangue , Zearalenona/sangue , Adulto , Cromatografia Líquida , Dieta , Estrogênios não Esteroides/metabolismo , Feminino , Abastecimento de Alimentos , Humanos , Limite de Detecção , Produtos da Carne , Menopausa , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Espectrometria de Massas em Tandem , Zearalenona/metabolismoRESUMO
A feeding experiment with piglets was performed to examine the efficacy of a wet preservation of Fusarium (FUS)-contaminated maize with sodium sulphite (SoS) based on deoxynivalenol (DON) and zearalenone (ZEN) residue levels in urine, bile and liquor and health traits of piglets. For this purpose, 80 castrated male piglets (7.57 ± 0.92 kg BW) were assigned to four treatment groups: CON- (control diet, with 0.09 mg DON and <0.01 mg ZEN/kg diet), CON+ (diet CON-, wet-preserved with 5 g SoS/kg maize; containing 0.05 mg DON and <0.01 mg ZEN/kg diet), FUS- (diet with mycotoxin-contaminated maize; containing 5.36 mg DON and 0.29 mg ZEN/kg diet), and FUS+ (diet FUS-, wet-preserved with 5 g SoS/kg maize; resulting in 0.83 mg DON and 0.27 mg ZEN/kg diet). After 42 d, 40 piglets (n = 10 per group) were sampled. A clear reduction of DON levels by approximately 75% was detected in all specimens of pigs fed diet FUS+. ZEN was detected in all urine, bile and liquor samples, while their metabolites were only detectable in urine and bile. Additionally, their concentrations were not influenced by SoS treatment. Among the health-related traits, feeding of FUS diets increased the total counts of leukocytes and segmented neutrophil granulocytes irrespective of SoS treatment. SoS treatment increased the total blood protein content slightly with a similar numerical trend in albumin concentration. These effects occurred at an obviously lower level in FUS-fed groups. Moreover, SoS treatment recovered the reduction of NO production induced by feeding diet FUS- indicating an effect on the redox level. As this effect only occurred in group FUS+, it is obviously related to the adverse effects of the Fusarium toxins. In conclusion, treatment of FUS-contaminated maize with SoS decreased the inner exposure with DON as indicated by the lower DON levels in various piglet specimens. However, health-related traits did not consistently reflect this decreased exposure.
Assuntos
Micotoxinas/metabolismo , Sulfitos/administração & dosagem , Sus scrofa/fisiologia , Tricotecenos/metabolismo , Zearalenona/metabolismo , Ração Animal/análise , Animais , Descontaminação , Dieta/veterinária , Fusarium/química , Masculino , Micotoxinas/sangue , Micotoxinas/urina , Distribuição Aleatória , Sus scrofa/sangue , Tricotecenos/sangue , Tricotecenos/urina , Zea mays/química , Zearalenona/sangue , Zearalenona/urinaRESUMO
This study aimed to investigate a potential modulatory effect of E. coli lipopolysaccharide (LPS) on the kinetics of deoxynivalenol (DON) and zearalenone (ZEN) after pre- or post-hepatic LPS administration to unravel the putative role of the liver. Fifteen barrows were fed a diet containing mycotoxin-contaminated maize (4.59 mg DON/kg feed, 0.22 mg ZEN/kg feed) for 29 days and equipped with pre-hepatic catheters (portal vein, "po") and post-hepatic catheters (jugular vein, "ju"), facilitating simultaneous infusion of LPS ("LPS group", 7.5 µg/kg body weight) or 0.9% sterile NaCl solution (control, "CON group", equivolumar to LPS group) and blood sampling. This resulted in three infusion groups, depending on infusion site: CONju-CONpo, CONju-LPSpo, and LPSju-CONpo. On day 29, pigs were fed their morning ration (700 g/pig) (-15 min), and blood samples were collected at regular intervals relative to infusion start. At 195 min, pigs were sacrificed and bile, urine, liquor, and liver samples collected. DON concentrations in jugular and portal blood decreased in both LPS-infused groups, whereas the ZEN concentrations increased, regardless of the treatment site. In liver tissue, a decrease of both toxin concentrations was observed in endotoxaemic pigs as well as a drop in hepatic conjugation, regardless of LPS entry site. In contrast to our hypothesis, DON and ZEN were not differently altered depending on the LPS-entry site. Neither the absorption nor the accumulation of DON and ZEN in different tissues differed significantly between animals which were infused with LPS via either the jugular or portal vein.
Assuntos
Endotoxemia/sangue , Lipopolissacarídeos/administração & dosagem , Suínos/sangue , Tricotecenos/sangue , Zearalenona/sangue , Ração Animal , Animais , Escherichia coli , Contaminação de Alimentos , Cinética , Tricotecenos/farmacocinética , Zearalenona/farmacocinéticaRESUMO
Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and ß-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC50 (µM) for DON, 3AcDON, ß-ZEL, α-ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC50 values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 µM.The in vivo screening (N = 49) revealed the occurrence of ZEN (N = 24), α-ZEL (N = 3), ß-ZEL (N = 37), DON, and DOM-1 (N = 2). The detected concentrations were much lower than the corresponding IC50 while the IC10 of DON and ß-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of ß-ZEL, α-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.
Assuntos
Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Tricotecenos/sangue , Tricotecenos/toxicidade , Zearalenona/sangue , Zearalenona/toxicidade , Animais , Análise Química do Sangue , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Cavalos , Concentração Inibidora 50 , MasculinoRESUMO
A long-term feeding experiment with dairy cows was performed to investigate the effects of feeding a Fusarium toxin contaminated (FUS) and a background-contaminated control (CON) ration with a mean concentrate feed proportion of 50% during the first 11 weeks after parturition (Groups FUS-50, CON-50, Period 1), and with concentrate feed proportions of 30% or 60% during the remaining 17 weeks (Groups CON-30, CON-60, FUS-30 and FUS-60, Period 2), on zearalenone (ZEN) residue levels in blood serum, milk, urine and bile. ZEN, α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL), zearalanone (ZAL), α-zearalanol (α-ZAL) and ß-zearalanol (ß-ZAL) were determined by HPLC with fluorescence detection. The ZEN concentrations of the rations fed to Groups CON-50, FUS-50 (Period 1), CON-30, CON-60, FUS-30 and FUS-60 (Period 2) amounted to 53.1, 112.7, 35.0, 24.4, 73.8 and 72.5 µg/kg dry matter, respectively. The concentrations of ZEN, α-ZEL, ß-ZEL, ZAN, α-ZAL and ß-ZAL in serum, urine and milk were lower than 1, 1, 4, 100, 50 and 200 ng/g, respectively, while ZEN, α-ZEL and ß-ZEL were detected in bile. Their levels changed with oral ZEN exposure in the course of the experiment and in a similar direction with concentrate feed proportion (Period 2 only). Thus the proportions of the individual ß-ZEL, α-ZEL and ZEN concentrations of their sum varied only in narrow ranges of 68-76%, 6-13% and 12-20%, respectively. Interestingly, the bile concentrations of ß-ZEL, α-ZEL and ZEN of Groups CON-60 and FUS-60 amounted to only approximately 50%, 45% and 62%, respectively, of those of Groups CON-30 and FUS-30 despite a similar or even lower ZEN exposure. The results indicate that conversion of ZEN to its detectable metabolites was not changed by different dietary concentrate feed proportions while their absolute levels were decreased. These findings might suggest concentrate feed proportion-dependent and rumen fermentation-mediated alterations in ZEN/metabolite degradation, and/or liver associated alterations in bile formation and turnover.
Assuntos
Ração Animal/análise , Bovinos/metabolismo , Dieta/veterinária , Zearalenona/metabolismo , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Resíduos de Drogas , Feminino , Leite/química , Zearalenona/sangue , Zearalenona/química , Zearalenona/urina , Zeranol/análogos & derivados , Zeranol/química , Zeranol/metabolismoRESUMO
The contamination of plant material with mycotoxins, in particular of the genus Fusarium, is common in the natural environment. Multiparous female wild boars are exposed to feed contaminated with zearalenone (ZEN) and deoxynivalenol throughout the year. The aim of this study was to determine the concentrations of the above mycotoxins in multiparous female wild boars and to describe their effect on the histological structure of the ovaries at the beginning of astronomical winter. Toxicological examinations revealed 0.291 ng/ml of ZEN, 0.406 ng/ml of α-zearalenol (α-ZEL), 0.392 ng/ml ß-zearalenol (ß-ZEL) and an absence of deoxynivalenol (values below the sensitivity of the method) in the blood plasma of multiparous female wild boars. Numerous ovarian follicles at various stages of development, characterized by different degree of damage, were observed. Numerous deformed resting ovarian follicles were noted directly under the epithelium, and signs of follicular atresia and hyalinization were observed. Blood vessels in the medulla of the ovary were dilated, which probably improved the distribution of ZEN in the ovaries. Higher substrate (ZEN) concentrations in the ovaries led to an insignificant increase in the staining intensity of 3ß-HSD and 17ß-HSD clusters. The observed changes could contribute to prolonging the initial stage of late anestrus in multiparous female wild boars.
Assuntos
Disruptores Endócrinos/toxicidade , Micotoxinas/toxicidade , Ovário/efeitos dos fármacos , Sus scrofa/fisiologia , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Disruptores Endócrinos/sangue , Disruptores Endócrinos/metabolismo , Monitoramento Ambiental , Ciclo Estral/efeitos dos fármacos , Feminino , Micotoxinas/sangue , Micotoxinas/metabolismo , Estações do Ano , Tricotecenos/sangue , Tricotecenos/metabolismo , Zearalenona/sangue , Zearalenona/metabolismoRESUMO
A sensitive and selective liquid chromatography tandem mass spectrometry method using negative electrospray ionisation (LC-ESI-MS/MS) was developed for the simultaneous determination of zearalenone (ZEN), deoxynivalenol (DON) and their metabolites α-zearalenol, ß-zearalenol, zearalanone, α-zearalanol, ß-zearalanol and de-epoxy-deoxynivalenol in pig serum. For method development, different sample preparation columns were tested for their suitability for extraction and clean up. Finally, preparation of serum samples was carried out using Oasis™ HLB solid-phase extraction (SPE) columns. The analyte concentrations were determined by the use of isotopically labelled internal standards (IS). The method was in-house validated for all analytes. Calibration graphs (0.3-480 ng/ml) were prepared and high degree of linearity was achieved (r ≥ 0.99). Results for method precision ranged between 2.7 and 21.5 % for inter-day and between 1.1 and 11.1 % for intra-day. The recoveries were in the range of 82-131 %. Limits of detection and quantification ranged 0.03-0.71 and 0.08-2.37 ng/ml, respectively. The method has been successfully used for quantitative determination of ZEN, DON and their metabolites in pig serum from a feeding trial with practically relevant ZEN and DON concentrations. This method is precise and reproducible and can be used as a multi-biomarker method to assess animal exposure to these mycotoxins and for diagnosis of intoxications.
Assuntos
Metabolômica/métodos , Tricotecenos/metabolismo , Zearalenona/metabolismo , Animais , Cromatografia Líquida , Feminino , Limite de Detecção , Reprodutibilidade dos Testes , Suínos , Espectrometria de Massas em Tandem , Tricotecenos/sangue , Zearalenona/sangueRESUMO
A feeding trial with dairy cows fed graded proportions of a Fusarium toxin contaminated maize containing mainly deoxynivalenol (DON) was carried out to relate the plasma levels of DON, zearalenone (ZEN) and their metabolites to the performance. German Holstein cows (n=30) were divided into three groups (n=10 in each): CON (0.02mgZEN and 0.07mgDON, per kg dry matter, DM), FUS-50 (0.33mg ZEN and 2.62mgDON, per kg DM), FUS-100 (0.66mgZEN and 5.24mgDON, per kg DM). The average performance level was characterised by daily DM intake, energy balance and milk yield which were not affected by the DON and ZEN levels in feed. DON, de-epoxy-DON (de-DON) and ZEN were detected simultaneously in all plasma samples. A linear relationship between toxin intake and plasma levels could be established. Moreover, a linear relationship between DON and de-DON concentration could be derived. It was concluded that DON and ZEN intake of 0.5mgZEN/kg and 5mgDON/kg (current guidance values) had no considerable effects on the performance parameter of dairy cows. Furthermore, increased plasma concentrations of ZEN, DON and de-DON may hint on toxin exposure through the diets.
Assuntos
Ração Animal , Indústria de Laticínios , Fusarium/isolamento & purificação , Tricotecenos/sangue , Zea mays/microbiologia , Zearalenona/sangue , Animais , BovinosRESUMO
The experiment involved 30 clinically healthy female Beagle dogs aged approximately 70 days with estimated initial body weight (BW) of 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was intoxicated with 50 µg zearalenone/kg BW per os for 42 days, group EII received 75 µg zearalenone/kg BW per os for 42 days, and the control group was administered placebo per os for 42 days. The animals were weighed, and blood samples for analyses of the concentrations of zearalenone, its metabolites, progesterone and 17ß-estradiol were collected seven times at seven-day intervals, one hour after mycotoxin administration. Biotransformation of zearalenone was observed in all groups throughout the experiment, and the highest percentage share of α-zearalenol was reported in group EII on the last five sampling dates (0.637-0.788 ng/ml, i.e. percentage share of 57.96-73.64%). The above had a significant influence on the non-physiological concentrations of progesterone and 17ß-estradiol in both experimental (E) groups throughout the experiment. The lowest progesterone levels (0.131 ng/ml) were observed in group EII during the last test, and high concentrations of 17ß-estradiol were found in group EII on the last two sampling dates (17.434 and 21.581 ng/ml, respectively) in comparison with control. Inhibited proliferation, manifested by a slower rate of body weight gain, was observed on the last but one day of zearalenone administration in both experimental groups. Our results indicate that NOAEL doses have stimulating/adaptive effects, whereas doses above NOAEL values suggest that even very low zearalenone doses can act as endocrine disruptors with regard to progesterone and 17ß-estradiol.
Assuntos
Cães/sangue , Estradiol/sangue , Progesterona/sangue , Zearalenona/farmacologia , Animais , Biotransformação , Cromatografia Líquida , Feminino , Espectrometria de Massas , Maturidade Sexual , Zearalenona/administração & dosagem , Zearalenona/sangue , Zearalenona/farmacocinéticaRESUMO
Concentration profile of zearalenone (ZON) and its metabolites in plasma, urine and faeces samples of horses fed with Fusarium toxin-contaminated oats is described. In plasma, ß-zearalenol (ß-ZOL) was detected at high levels on day 10 of the study (3.21-6.24 µg/l). ß-Zearalenol and α-zearalenol were the major metabolites in urine. Zearalenone, α-ZOL and ß-ZOL were predominantly found in faeces. Zearalanone could also be detected in urine (1.34-5.79 µg/l) and faeces (1 µg/kg). The degree of glucuronidation was established in all sample types, approximately 100% in urine and plasma. Low per cent of glucuronidation (4-15%) was found in faeces samples. The results indicate the main conversion of ZON into ß-ZOL in horse. This finding could explain why horse is not susceptible to ZON in comparison with swine which produce α-ZOL as a predominant metabolite.
Assuntos
Fezes/química , Fusarium/metabolismo , Cavalos/metabolismo , Zearalenona/sangue , Zearalenona/metabolismo , Animais , Feminino , Cavalos/sangue , Cavalos/urina , Especificidade da Espécie , Zearalenona/química , Zearalenona/urinaRESUMO
Mycotoxins lead to economic losses in animal production. A way to counteract mycotoxicosis is the use of detoxifiers. The European Food Safety Authority stated that the efficacy of detoxifiers should be investigated based on toxicokinetic studies. Little information is available on the absolute oral bioavailability and the toxicokinetic parameters of deoxynivalenol, T-2 and zearalenone in broilers. Toxins were administered intravenously and orally in a two-way cross-over design. For deoxynivalenol a bolus of 0.75mg/kg BW was administered, for T-2 toxin 0.02mg/kg BW and for zearalenone 0.3mg/kg BW. Blood was collected at several time points. Plasma levels of the mycotoxins and their metabolite(s) were quantified using LC-MS/MS methods and toxicokinetic parameters were analyzed. Deoxynivalenol has a low absolute oral bioavailability (19.3%). For zearalenone and T-2 no plasma levels above the limit of quantification were observed after an oral bolus. Volumes of distribution were recorded, i.e. 4.99, 0.14 and 22.26L/kg for deoxynivalenol, T-2 toxin and zearalenone, respectively. Total body clearance was 0.12, 0.03 and 0.48L/minkg for deoxynivalenol, T-2 toxin and zearalenone, respectively. After IV administration, T-2 toxin had the shortest elimination half-life (3.9min), followed by deoxynivalenol (27.9min) and zearalenone (31.8min).
Assuntos
Galinhas , Toxina T-2/farmacocinética , Tricotecenos/farmacocinética , Zearalenona/farmacocinética , Administração Oral , Ração Animal , Animais , Disponibilidade Biológica , Cromatografia Líquida , Meia-Vida , Injeções Intravenosas , Farmacocinética , Toxina T-2/sangue , Espectrometria de Massas em Tandem , Tricotecenos/sangue , Zearalenona/sangueRESUMO
A sensitive and specific method for the quantitative determination of zearalenone (ZEN) and its major metabolites (α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL), α-zearalanol (α-ZAL), ß-zearalanol (ß-ZAL) and zearalanone (ZAN)) in animal plasma using liquid chromatography combined with heated electrospray ionization (h-ESI) tandem mass spectrometry (LC-MS/MS) and high-resolution Orbitrap(®) mass spectrometry ((U)HPLC-HR-MS) is presented. The sample preparation was straightforward, and consisted of a deproteinization step using acetonitrile. Chromatography was performed on a Hypersil Gold column (50 mm × 2.1 mm i.d., dp: 1.9 µm, run-time: 10 min) using 0.01% acetic acid in water (A) and acetonitrile (B) as mobile phases. Both mass spectrometers were operated in the negative h-ESI mode. The method was in-house validated for all analytes: matrix-matched calibration graphs were prepared and good linearity (r≥0.99) was achieved over the concentration range tested (0.2-200 ng mL(-1)). Limits of quantification (LOQ) in plasma were between 0.2 and 5 ng mL(-1) for all compounds. Limits of detection in plasma ranged from 0.004 to 0.070 ng mL(-1). The results for the within-day and between-day precision, expressed as relative standard deviation (RSD), fell within the maximal RSD values (within-day precision: RSD(max)=2((1-0.5logConc)) x 2/3; between-day precision: RSD(max)=2((1-0.5logConc))). The accuracy fell within -50% to +20% (concentrations <1 ng mL(-1)), -30% to +10% (concentrations between 1 and 10 ng mL(-1)) or -20% to +10% (concentrations >10 ng mL(-1)) of the theoretical concentration. The method has been successfully used for the quantitative determination of ZEN in plasma samples from broiler chickens and pigs. α-ZEL and ß-ZEL were the only metabolites that could be detected, but the concentrations were around the LOQ levels. The intact ZEN-glucuronide conjugate could be detected using the (U)HPLC-HR-MS instrument. A good correlation (r(2)=0.9979) was observed between the results for ZEN obtained with the LC-MS/MS and (U)HPLC-HR-MS instruments. The results prove the usefulness of the developed method for application in the field of toxicokinetic analysis and for exposure assessment of mycotoxins.
Assuntos
Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Zearalenona/sangue , Animais , Galinhas , Limite de Detecção , Suínos , Zearalenona/metabolismoRESUMO
Zearalenone, a mycotoxin biosynthesized by various Fusarium fungi, is widely found as a contaminant in grains and animal feeds. This study describes a rapid and sensitive LC/MS/MS assay method for the quantification of zearalenone in rat serum. The assay was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The multiple reaction monitoring was based on the transition of m/z 317.0 --> 130.9 for zearalenone and 319.0 --> 204.8 for zearalanone (internal standard). The assay utilized a single liquid-liquid extraction with t-butyl methyl ether and isocratic elution, and the LLOQ was 0.5 ng/mL using 0.1 mL rat serum. The assay was linear over a concentration range from 0.5 to 200 ng/mL, with correlation coefficients >0.9996. The mean intra- and inter-day assay accuracy was 101.2-112.9 and 96.3-108.0%, respectively. The mean intra- and inter-day precision was between 1.3-7.6 and 3.6-10.6%, respectively. The developed assay was applied to a pharmacokinetic study after a bolus intravenous injection of zearalenone in rats.