RESUMO
Mycotoxins are potent fungal toxins that frequently contaminate agricultural crops and foods. Mycotoxin exposure is frequently reported in humans, and children are known to be particularly at risk of exceeding safe levels of exposure. Urinary biomonitoring is used to assess overall dietary exposure to multiple mycotoxins. This study aims to quantify multi-mycotoxin exposure in UK children and to identify major food groups contributing to exposure. Four repeat urine samples were collected from 29 children (13 boys and 16 girls, aged 2.4-6.8 years), and food diaries were recorded to assess their exposure to eleven mycotoxins. Urine samples (n = 114) were hydrolysed with ß-glucuronidase, enriched through immunoaffinity columns and analysed by LC-MS/MS for deoxynivalenol (DON), nivalenol (NIV), T-2/HT-2 toxins, zearalenone (ZEN), ochratoxin A (OTA) and aflatoxins. Food diaries were analysed using WinDiet software, and the daily intake of high-risk foods for mycotoxin contamination summarised. The most prevalent mycotoxins found in urine samples were DON (95.6% of all samples), OTA (88.6%), HT-2 toxin (53.5%), ZEN (48.2%) and NIV (26.3%). Intake of total cereal-based foods was strongly positively associated with urinary levels of DON and T-2/HT-2 and oat intake with urinary T-2/HT-2. Average daily mycotoxin excretion ranged from 12.10 µg/d (DON) to 0.03 µg/d (OTA), and co-exposure to three or more mycotoxins was found in 66% of samples. Comparing mycotoxin intake estimates to tolerable daily intakes (TDI) demonstrates frequent TDI exceedances (DON 34.2% of all samples, T-2/HT-2 14.9%, NIV 4.4% and ZEN 5.2%). OTA was frequently detected at low levels. When mean daily OTA intake was compared to the reference value for non-neoplastic lesions, the resulting Margin of Exposure (MoE) of 65 was narrow, indicating a health concern. In conclusion, this study demonstrates frequent exposure of UK children to multiple mycotoxins at levels high enough to pose a health concern if exposure is continuous.
Assuntos
Exposição Dietética , Contaminação de Alimentos , Micotoxinas , Humanos , Masculino , Feminino , Criança , Micotoxinas/urina , Micotoxinas/análise , Pré-Escolar , Reino Unido , Exposição Dietética/análise , Contaminação de Alimentos/análise , Monitoramento Biológico , DietaRESUMO
SCOPE: Cardiovascular health is strongly influenced by diet. Zinc has antioxidant and anti-inflammatory properties but its long-term influence on vascular health at dietary intake levels relevant to the human population in developed countries has not been studied. We investigated the influence of suboptimal zinc intake in a Western-type diet on the development of vascular inflammation and arterial plaque in apoE knock-out (AEKO) mice. METHODS AND RESULTS: Weanling AEKO and wild-type (WT) controls were given high saturated fat (21% w/w) and high cholesterol (0.15%) semi-synthetic diets containing 3 or 35 mg Zn/kg (AEKO and WT) or 8 mg Zn/kg (AEKO only) for over 6 months. AEKO mice on zinc intakes of 3 and 8 mg Zn/kg (suboptimal zinc) developed significantly (p < 0.05) more aortic plaque than AEKO mice consuming 35 mg Zn/kg (adequate zinc). Circulating levels of interleukin-1ß, interleukin-6 and soluble vascular adhesion molecule-1 were significantly (p < 0.05) raised at the lowest zinc intake in AEKO mice, as compared to zinc-adequate controls. Plasma total cholesterol and total protein were also significantly (p < 0.05) increased at the lowest zinc intake. CONCLUSION: We propose that suboptimal dietary zinc intake raises circulating pro-atherogenic lipoprotein levels that promote vascular inflammation and enhance arterial plaque formation.
Assuntos
Aterosclerose/etiologia , Dieta/efeitos adversos , Modelos Animais de Doenças , Vasculite/etiologia , Zinco/deficiência , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Calcinose/etiologia , Calcinose/imunologia , Calcinose/patologia , Calcinose/prevenção & controle , Dieta Aterogênica/efeitos adversos , Interleucinas/sangue , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/prevenção & controle , Distribuição Aleatória , Índice de Gravidade de Doença , Molécula 1 de Adesão de Célula Vascular/sangue , Vasculite/sangue , Vasculite/imunologia , Vasculite/prevenção & controle , Zinco/administração & dosagem , Zinco/uso terapêuticoRESUMO
SCOPE: Cardiovascular disease is the major cause of death in the world. Low dietary folate, elevated homocysteine, and high circulating cholesterol are risk factors. METHODS AND RESULTS: We investigated whether folate and/or B vitamin deficiency would change lipoprotein and fatty acid metabolism and lipid accumulation in the aorta adventitia of ApoE null mice. Mice (n = 10 per group) were fed a control (C; 4%) or high saturated fat (HF; 21%), and high cholesterol (0.15%) diet for 16 weeks. Folate (F-) or folate, B6 and B12 deficiency (F-B-) were imposed on these diets. Feeding a HF diet increased plasma and liver total cholesterol and HDL cholesterol (two- to threefold; p < 0.05). Total cholesterol increased (twofold; p < 0.05) in aorta adventitial lipid in response to HF. Feeding a diet depleted of folate and B vitamins (F-B-) significantly increased cholesterol accumulation in both liver and aorta adventitial lipid (approximately 50-70%; p < 0.05). Moreover, the proportions of fatty acids in hepatic and adventitial lipid was significantly changed by B vitamin depletion, measured as an increase in saturated fatty acids (approximately 15%) and a decrease (approximately 11%) in monounsaturated fatty acids (p < 0.05). CONCLUSION: B vitamin deficiency perturbs lipid metabolism in ApoE null mice, causing accumulation of proatherogenic cholesterol and fatty acids in the aorta adventitia.
Assuntos
Aorta/metabolismo , Aterosclerose/etiologia , Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Lipoproteínas/metabolismo , Deficiência de Vitaminas do Complexo B/fisiopatologia , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Colesterol/sangue , Colesterol/metabolismo , Dieta Aterogênica/efeitos adversos , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Hiper-Homocisteinemia/etiologia , Lipoproteínas/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Índice de Gravidade de Doença , Deficiência de Vitaminas do Complexo B/sangue , Deficiência de Vitaminas do Complexo B/metabolismoRESUMO
The kinetics of zinc absorption, metabolism and excretion is extensively studied by nutritionists. Stable isotopes of zinc can be used to identify body zinc compartments that have different turnover kinetics. Since the compartments might belong to physiological subsections of different organs, there is a need for microsampling analysis to determine isotope ratios of the trace element zinc in tissue samples. Here, we study the feasibility to use laser ablation coupled to quadrupole ICP-MS for the determination of zinc tracers given to rats at different time points with the aim to generate isotope ratio bioimages of heart tissue. A double tracer ((70)Zn and (67)Zn) experiment with rats was designed to label the exchangeable zinc pool as well as the stable zinc pool. The isotope ratios determined by laser ablation ICP-MS were evaluated by additional measurements of tissue digests. Accumulated tracers which made up more than 0.1% of total zinc could be identified in the tissues of the treated rats. It was established that at least 50 measurements from the microsampling were necessary to distinguish between controls and a tracer treated rat resulting in reduced resolution of the bioimage. With the parameters used, features in the tissue thin sections of at least 250 µm(2) in size are necessary to detect the incorporation of a tracer. When different time points have to be measured, higher precisions are required and therefore a larger area needs to be ablated (1 mm(2)). Using the bioimages and pool measurements from one physiological feature, it was possible to show that the aorta cell walls incorporate the zinc tracer at the different time points.
Assuntos
Terapia a Laser/métodos , Espectrometria de Massas/métodos , Isótopos de Zinco/química , Animais , Transporte Biológico , Cinética , Fígado/química , Fígado/metabolismo , Masculino , Microtomia , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Ratos , Distribuição Tecidual , Isótopos de Zinco/metabolismoRESUMO
Long-chain n-3 PUFA from fish oil protect against death from CHD but mechanisms are not well understood. Preliminary results indicate that fish oil may affect the enzyme soluble epoxide hydrolase (sEH) and influence inflammatory pathways in a time-dependent manner. In the present study male apoE knockout (Apoe-/-) mice were randomised to three dietary groups receiving a high-fat high-cholesterol diet supplemented with 2 % (w/w) high-oleic acid sunflower-seed (HOSF) oil, DHA oil or fish oil. Livers and proximal aortas were collected on day 2 and on weeks 1, 2, 4 and 10 to determine hepatic sEH levels, hepatic fatty acid composition, hepatic proteome and atherosclerotic plaque size in the aortic root. Intervention with fish oil, but not with DHA, resulted in significantly lower levels of hepatic sEH levels with time compared with HOSF oil. DHA and fish oil caused differential regulation of thirty-five hepatic proteins which were mainly involved in lipoprotein metabolism and oxidative stress. All mice developed atherosclerosis without differences in plaque size between the three groups. Thus EPA may be responsible for lowering levels of hepatic sEH and both fish oil and DHA could beneficially affect lipoprotein metabolism and oxidative stress.