Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression

Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 mu g pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-alpha, IL-1 beta, IL-6, IFN-gamma) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-gamma and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1. (C) 2008 Elsevier Inc. All rights reserved.

Spatial distribution of arsenic and temporal variation of its concentration in rice

P>In order to gain insights into the transport and distribution of arsenic (As) in intact rice (Oryza sativa) plants and its unloading into the rice grain, we investigated the spatial distribution of As and the temporal variation of As concentration in whole rice plants at different growth stages. To the best of our knowledge, this is the first time that such a study has been performed.

Inductively coupled plasma mass spectroscopy (ICP-MS) and high-performance liquid chromatography (HPLC)-ICP-MS were used to analyze total As concentration and speciation. Moreover, synchrotron-based X-ray fluorescence (SXRF) was used to investigate in situ As distribution in the leaf, internode, node and grain.

Total As concentrations of vegetative tissues increased during the 2 wk after flowering. The concentration of dimethylarsinic acid (DMA) in the caryopsis decreased progressively with its development, whereas inorganic As concentration remained stable. The ratios of As content between neighboring leaves or between neighboring internodes were c. 0.6. SXRF revealed As accumulation in the center of the caryopsis during its early development and then in the ovular vascular trace.

These results indicate that there are different controls on the unloading of inorganic As and DMA; the latter accumulated mainly in the caryopsis before flowering, whereas inorganic As was mainly transported into the caryopsis during grain filling. Moreover, nodes appeared to serve as a check-point in As distribution in rice shoots.

Inorganic arsenic in Chinese food and its cancer risk

Even moderate arsenic exposure may lead to health problems, and thus quantifying inorganic arsenic (iAs) exposure from food for different population groups in China is essential. By analyzing the data from the China National Nutrition and Health Survey (CNNHS) and collecting reported values of iAs in major food groups, we developed a framework of calculating average iAs daily intake for different regions of China. Based on this framework, cancer risks from As in food was deterministically and probabilistically quantified. The article presents estimates for health risk due to the ingestion of food products contaminated with arsenic. Both per individual and for total population estimates were obtained. For the total population, daily iAs intake is around 42 mu g day(-1), and rice is the largest contributor of total iAs intake accounting for about 60%. Incremental lifetime cancer risk from food iAs intake is 106 per 100,000 for adult individuals and the median population cancer risk is 177 per 100,000 varying between regions. Population in the Southern region has a higher cancer risk than that in the Northern region and the total population. Sensitive analysis indicated that cancer slope factor, ingestion rates of rice, aquatic products and iAs concentration in rice were the most relevant variables in the model, as indicated by their higher contribution to variance of the incremental lifetime cancer risk. We conclude that rice may be the largest contributor of iAs through food route for the Chinese people. The population from the South has greater cancer risk than that from the North and the whole population. (C) 2011 Elsevier Ltd. All rights reserved.

Arsenic Contents in Spanish Infant Rice, Pureed Infant Foods, and Rice

It seems there is a positive correlation between rice content and arsenic level in foods. This is of extraordinary importance for infants below 1 y of age because their diet is very limited and in some cases is highly dependent on rice-based products; this is particularly true for infants with the celiac disease because they have no other option than consume gluten-free products, such as rice or corn. Arsenic contents were significantly higher (P <0.001) in gluten-free infant rice (0.057 mg kg-1) than in products with gluten, based on a mixture of cereals (0.024 mg kg-1). Besides, especial precaution must be taken when preparing rice-based products at home, because arsenic content in Spanish rice was high, with levels being above 0.3 mg kg-1 in some cases.

Urinary excretion of arsenic following rice consumption

Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) similar to 40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis. (C) 2014 Elsevier Ltd. All rights reserved.

Arsenic Speciation and Localization in Horticultural Produce Grown in a Historically Impacted Mining Region

A field and market basket study (similar to 1300 samples) of locally grown fruits and vegetables from historically mined regions of southwest (SW) England (Cornwall and Devon), and as reference, a market basket study of similarly locally grown produce from the northeast (NE) of Scotland (Aberdeenshire) was conducted to determine the concentration of total and inorganic arsenic present in produce from these two geogenically different areas of the U.K. On average 98.5% of the total arsenic found was present in the inorganic form. For both the market basket and the field survey, the highest total arsenic was present in open leaf structure produce (i.e., kale, chard, lettuce, greens, and spinach) being most likely to soil/dust contamination of the open leaf structure. The concentration of total arsenic in potatoes, swedes, and carrots was lower in peeled produce compared to unpeeled produce. For baked potatoes, the concentration of total arsenic in the skin was higher compared to the total arsenic concentration of the potato flesh, this difference in localization being confirmed by laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS). For all above ground produce (e.g., apples), peeling did not have a significant effect on the concentration of total arsenic present.

Methylated Arsenic Species in Rice:Geographical Variation, Origin, and Uptake Mechanisms

Rice is a major source of inorganic arsenic (iAs) in the human diet because paddy rice. efficient at accumulating As Rice As speciation is dominated by iAs and dimethylarsinic acid (DMA). Here we review the global pattern in rice As speciation and the factors causing the variation. Rice produced in Asia shows a strong linear relationship between iAs and total As concentration with a slope of 0.78. Rice produced in Europe and the United States shows a more variable, but generally hyperbolic relationship with DMA being predominant in U.S. rice. Although there is significant genotypic variation in grain As speciation, the regional Variations are primarily attributed to environmental factors. Emerging evidence also indicates that methylated. As species in rice are derived from the soil, while rice plants lack the As methylation ability. Soil flooding and additions of organic matter increase microbial methylation of As, although the microbial community responsible for methylafion is poorly understood. Compared with iAs, methylated As species are taken up by rice roots less efficiently but are transported to the grain much, more efficiently, which may be an important factor responsible for the spikelet sterility disorder (straight head disease) in rice. DMA is a weak carcinogen, but the level of ingestion from rice consumption is much lower than that of concern. Questions that require further investigations are identified.

Seasonal and geographical differences in aflatoxin exposures in Senegal

The aim of the study was to determine the geographical and seasonal variations in aflatoxin dietary exposure levels in adults from Senegal. A total of 168 adults (50% male) were recruited from three districts: Nioro du Rip (n=90), located in the Sudan Savannah agro-ecological zone where rainfall is sufficient for groundnut growth; Saint-Louis (n=40) and Mboro (n=38), located in the Sahel zone where groundnuts are produced under irrigated conditions. Diet information and samples were collected at groundnut harvest and post-harvest seasons. Plasma aflatoxin-albumin adducts (AF-alb) and total aflatoxin in household groundnut samples were measured by ELISA and a quantitative thin layer chromatography method, respectively. The blood AF-alb geometric mean was 45.7 pg/mg albumin (range 5.5-588.2 pg/mg). Nioro du Rip had a higher AF-alb level at harvest than Saint-Louis and Mboro (80.0 vs 15.6 and 33.3 pg/mg, P<0.001). Similar trends were observed at post-harvest (P<0.05). Seasonal trends were not consistent across the districts as Nioro du Rip had a higher AF-alb level at harvest than post-harvest (80.0 vs 58.6 pg/mg, P=0.026), whereas Saint-Louis had a higher level at post-harvest than harvest (25.6 vs 15.6 pg/mg, P=0.032). It is clear that aflatoxin exposure is prevalent in adults from Senegal and that season and geographical location are strong determinants of aflatoxin exposure.

Développement d’outils utilisant la surveillance biologique pour évaluer l’exposition et les risques pour la santé : application au méthylmercure et au sélénium

Dans une perspective d’analyse des risques pour la santé publique, l’estimation de l’exposition revêt une importance capitale. Parmi les approches existantes d’estimation de l’exposition, l’utilisation d’outils, tels que des questionnaires alimentaires, la modélisation toxicocinétique ou les reconstructions de doses, en complément de la surveillance biologique, permet de raffiner les estimations, et ainsi, de mieux caractériser les risques pour la santé. Ces différents outils et approches ont été développés et appliqués à deux substances d’intérêt, le méthylmercure et le sélénium en raison des effets toxiques bien connus du méthylmercure, de l’interaction entre le méthylmercure et le sélénium réduisant potentiellement ces effets toxiques, et de l’existence de sources communes via la consommation de poisson. Ainsi, l’objectif général de cette thèse consistait à produire des données cinétiques et comparatives manquantes pour la validation et l’interprétation d’approches et d’outils d’évaluation de l’exposition au méthylmercure et au sélénium. Pour ce faire, l’influence du choix de la méthode d’évaluation de l’exposition au méthylmercure a été déterminée en comparant les apports quotidiens et les risques pour la santé estimés par différentes approches (évaluation directe de l’exposition par la surveillance biologique combinée à la modélisation toxicocinétique ou évaluation indirecte par questionnaire alimentaire). D’importantes différences entre ces deux approches ont été observées : les apports quotidiens de méthylmercure estimés par questionnaires sont en moyenne six fois plus élevés que ceux estimés à l’aide de surveillance biologique et modélisation. Ces deux méthodes conduisent à une appréciation des risques pour la santé divergente puisqu’avec l’approche indirecte, les doses quotidiennes estimées de méthylmercure dépassent les normes de Santé Canada pour 21 des 23 volontaires, alors qu’avec l’approche directe, seulement 2 des 23 volontaires sont susceptibles de dépasser les normes. Ces différences pourraient être dues, entre autres, à des biais de mémoire et de désirabilité lors de la complétion des questionnaires. En outre, l’étude de la distribution du sélénium dans différentes matrices biologiques suite à une exposition non alimentaire (shampoing à forte teneur en sélénium) visait, d’une part, à étudier la cinétique du sélénium provenant de cette source d’exposition et, d’autre part, à évaluer la contribution de cette source à la charge corporelle totale. Un suivi des concentrations biologiques (sang, urine, cheveux et ongles) pendant une période de 18 mois chez des volontaires exposés à une source non alimentaire de sélénium a contribué à mieux expliciter les mécanismes de transfert du sélénium du site d’absorption vers le sang (concomitance des voies régulées et non régulées). Ceci a permis de montrer que, contrairement au méthylmercure, l’utilisation des cheveux comme biomarqueur peut mener à une surestimation importante de la charge corporelle réelle en sélénium en cas de non contrôle de facteurs confondants tels que l’utilisation de shampoing contenant du sélénium. Finalement, une analyse exhaustive des données de surveillance biologique du sélénium issues de 75 études publiées dans la littérature a permis de mieux comprendre la cinétique globale du sélénium dans l’organisme humain. En particulier, elle a permis le développement d’un outil reliant les apports quotidiens et les concentrations biologiques de sélénium dans les différentes matrices à l’aide d’algorithmes mathématiques. Conséquemment, à l’aide de ces données cinétiques exprimées par un système d’équations logarithmiques et de leur représentation graphique, il est possible d’estimer les apports quotidiens chez un individu à partir de divers prélèvements biologiques, et ainsi, de faciliter la comparaison d’études de surveillance biologique du sélénium utilisant des biomarqueurs différents. L’ensemble de ces résultats de recherche montre que la méthode choisie pour évaluer l’exposition a un impact important sur les estimations des risques associés. De plus, les recherches menées ont permis de mettre en évidence que le sélénium non alimentaire ne contribue pas de façon significative à la charge corporelle totale, mais constitue un facteur de confusion pour l’estimation de la charge corporelle réelle en sélénium. Finalement, la détermination des équations et des coefficients reliant les concentrations de sélénium entre différentes matrices biologiques, à l’aide d’une vaste base de données cinétiques, concourt à mieux interpréter les résultats de surveillance biologique.

The challenges for molecular nutrition research 1: linking genotype to healthy nutrition

Nutrition science finds itself at a major crossroad. On the one hand we can continue the current path, which has resulted in some substantial advances, but also many conflicting messages which impair the trust of the general population, especially those who are motivated to improve their health through diet. The other road is uncharted and is being built over the many exciting new developments in life sciences. This new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realisation that nutrition is essentially a gene - environment interaction science. This review on the relation between genotype, diet and health is the first of a series dealing with the major challenges in molecular nutrition, analyzing the foundations of nutrition research. With the unravelling of the human genome and the linking of its variability to a multitude of phenotypes from " healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. Classical genetic approaches applied so far in medical genetics have steered away from incorporating dietary effects in their models and paradoxically, most genetic studies analyzing diet-associated phenotypes and diseases simply ignore diet. Yet, a modest but increasing number of studies are accounting for diet as a modulator of genetic associations. These range from observational cohorts to intervention studies with prospectively selected genotypes. New statistical and bioinformatics approaches are becoming available to aid in design and evaluation of these studies. This review discusses the various approaches used and provides concrete recommendations for future research.

The acrylamide problem: a plant and agronomic science issue.

Acrylamide, a chemical that is probably carcinogenic in humans and has neurological and reproductive effects, forms from free asparagine and reducing sugars during high-temperature cooking and processing of common foods. Potato and cereal products are major contributors to dietary exposure to acrylamide and while the food industry reacted rapidly to the discovery of acrylamide in some of the most popular foods, the issue remains a difficult one for many sectors. Efforts to reduce acrylamide formation would be greatly facilitated by the development of crop varieties with lower concentrations of free asparagine and/or reducing sugars, and of best agronomic practice to ensure that concentrations are kept as low as possible. This review describes how acrylamide is formed, the factors affecting free asparagine and sugar concentrations in crop plants, and the sometimes complex relationship between precursor concentration and acrylamide-forming potential. It covers some of the strategies being used to reduce free asparagine and sugar concentrations through genetic modification and other genetic techniques, such as the identification of quantitative trait loci. The link between acrylamide formation, flavour, and colour is discussed, as well as the difficulty of balancing the unknown risk of exposure to acrylamide in the levels that are present in foods with the well-established health benefits of some of the foods concerned. Key words: Amino acids, asparagine, cereals, crop quality, food safety, Maillard reaction, potato, rye, sugars, wheat.

A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment

Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD50 dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of 14C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD50. The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail.

Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet: the FLAVURS trial in adults: the FLAVURS trial

The present study aims to investigate the dose dependent effects of consuming diets enriched in flavonoid-rich and flavonoid-poor fruits and vegetables on the urine metabolome of adults who had a C1.5 fold increased risk of cardiovascular diseases. A single-blind, dose-dependent, parallel randomized controlled dietary intervention was conducted where volunteers (n = 126) were randomly assigned to one of three diets: high flavonoid diet, low flavonoid diet or habitual diet as a control for 18 weeks. High resolution LC– MS untargeted metabolomics with minimal sample cleanup was performed using an Orbitrap mass spectrometer. Putative biomarkers which characterize diets with high and low flavonoid content were selected by state-of-the-art data analysis strategies and identified by HR-MS and HR-MS/MS assays. Discrimination between diets was observed by application of two linear mixedmodels: one including a diet-time interaction effect and the second containing only a time effect. Valerolactones, phenolic acids and their derivatives were among sixteen biomarkers related to the high flavonoid dietary exposure. Four biomarkers related to the low flavonoid diet belonged to the family of phenolic acids. For the first time abscisic acid glucuronide was reported as a biomarker after a dietary intake, however its origins have to be examined by future hypothesis driven experiments using a more targeted approach. This metabolomic analysis has identified a number of dose dependent urinary biomarkers (i.e. proline betaine or iberin-N-acetyl cysteine), which can be used in future observation and intervention studies to assess flavonoids and nonflavonoid phenolic intakes and compliance to fruit and vegetable intervention.

Immunomodulatory effects of Pteridium aquilinum on natural killer cell activity and select aspects of the cellular immune response of mice

Pteridium aquilinum (bracken fern) is one of the most common plants. Epidemiological studies have revealed a higher risk of certain types of cancers (i.e., esophageal, gastric) in people who consume bracken fern directly ( as crosiers or rhizomes) or indirectly through the consumption of milk from livestock that fed on the plant. In animals, evidence exists regarding the associations between chronic bracken fern intoxication, papilloma virus infection, and the development of carcinomas. While it is possible that some carcinogens in bracken fern could be responsible for these cancers in both humans and animals, it is equally plausible that the observed increases in cancers could be related to induction of an overall immunosuppression by the plant/its various constituents. Under the latter scenario, normal tumor surveillance responses against nascent (non-bracken-induced) cancers or responses against viral infections ( specifically those linked to induction of cancers) might be adversely impacted by continuous dietary exposure to this plant. Therefore, the overall objective of this study was to evaluate the immunomodulatory effects of bracken fern following daily ingestion of its extract by a murine host over a period of 14 ( or up to 30) days. In C57BL/6 mice administered ( by gavage) the extract, histological analyses revealed a significant reduction in splenic white pulp area. Among a variety of immune response parameters/functions assessed in these hosts and isolated cells, both delayed-type hypersensitivity (DTH) analysis and evaluation of IFN gamma. production by NK cells during T(H)1 priming were also reduced. Lastly, the innate response in these hosts-assessed by analysis of NK cell cytotoxic functionality-was also diminished. The results here clearly showed the immunosuppressive effects of P. aquilinum and that many of the functions that were modulated could contribute to the increased risk of cancer formation in exposed hosts.

Arsenic and heavy metal contamination of rice, pulses and vegetables grown in Samta village, Bangladesh

Arsenic contaminated water from tube wells has become the major health problem threatening millions of people in Bangladesh. However, the arsenic (As) contaminated water is not just used for drinking, it is used to irrigate crops, and to wash and prepare food. Contamination of agricultural soils by long-term irrigation with As contaminated water can lead to contamination and phyto-accumulation of the food crops with As and other toxic metals. As a consequence, dietary exposure to As and other toxic metals may contribute substantially to the adverse health effects caused by the contaminated tube wells in Bangladesh. Various vegetables, rice, pulses and the grass pea were sampled in Samta village in the Jessore district of Bangladesh and screened for As, Cd, Cu, Pb and Zn by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. These local food crops provide the majority of the nutritional intake of the people in this area and are of great importance to their overall health. In general, our data show the potential for some vegetables to accumulate heavy metals with concentrations of Pb greater than Cd. The concentrations of As and Cd were higher in vegetables than in rice and pulses. The concentration of Pb was generally higher in rice than in pulses and vegetables. However, some vegetables such as bottle ground leaf, ghotkol, taro, eddoe and elephant foot had much higher concentrations of Pb. Other leafy and root vegetables contained higher concentrations oJ2n and Cu. Rice grown at Samta had increased Pb and As, but, considering an average daily intake of only 260 g rice per person per day, only the Pb is at concentrations which would be a health hazard/or human consumption.