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Mycotoxins and Human Diseases 2015

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A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 July 2015) | Viewed by 71920

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Dr. Paul Turner

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School of Public Health, University of Maryland, College Park, MD, USA
Interests: dietary toxins; child health; interventions; developing countries; cancer; malnutrition; cereals; mycotoxins; exposure assessment; epidemiology; food toxicology; growth faltering; stunting; liver cancer; gastrointestinal toxicity
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Dear Colleagues,

Mycotoxins are the secondary metabolites of a variety of fungal species. Many thousands of mycotoxins exist. Their contributions to animal and human health depend on both the potency and frequency with which they contaminate feeds and foodstuffs. Certain mycotoxins can also be carried in the air, for example in grain mills or in water damaged buildings. Despite the availability of numerous impressive analytical tools that have the capacity to detect exposure at high, modest, and low levels, there remains limited data concerning the health effects of mycotoxins (with the exception on data for aflatoxins). There is a desperate need for biomarker driven research for many of the most frequent mycotoxins contaminants. In this Special Issue, manuscripts are invited that provide critical data on exposure assessment, health outcomes/epidemiology, and interventions in relation to single or multiple mycotoxins, especially where data is generated in world regions with high risks of exposure. Emphasis will be placed on studies concerning disease outcomes, or if such studies concern interventions, the relevant disease reductions. In addition to specific disease end points, submitted papers can also include studies that investigate how mycotoxin exposures modifies biomarkers of affect. These studies may include, but are not limited to, aflatoxins, fumonisins, ochratoxins, trichothecenes, zearalenones, and their mixtures. Toxicokinetic data, at realistic doses, in animals and humans will also be considered, along with novel mechanistic data from animals or cell culture models; such studies may predict molecular targets in humans.

Dr Paul C Turner
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

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Related Special Issue

Mycotoxins and Human Diseases in Toxins (2 articles)

Keywords

mycotoxins
exposure assessment
aflatoxins
fumonisins
ochratoxin
trichothecenes
epidemiology
interventions
epidemiology

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Impact of Human Metabolism on the Toxicological Effects of Mycotoxins in Toxins (4 articles)

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611 KiB

Open AccessArticle

Temporal Variation and Association of Aflatoxin B₁ Albumin-Adduct Levels with Socio-Economic and Food Consumption Factors in HIV Positive Adults

by Pauline E. Jolly, Tomi F. Akinyemiju, Megha Jha, Inmaculada Aban, Andrea Gonzalez-Falero and Dnika Joseph

Toxins 2015, 7(12), 5129-5140; https://doi.org/10.3390/toxins7124868 - 30 Nov 2015

Cited by 12 | Viewed by 5394

Abstract

The association between aflatoxin exposure and alteration in immune responses observed in humans suggest that aflatoxin could suppress the immune system and work synergistically with HIV to increase disease severity and progression to AIDS. No longitudinal study has been conducted to assess exposure to aflatoxin (AF) among HIV positive individuals. We examined temporal variation in AFB₁ albumin adducts (AF-ALB) in HIV positive Ghanaians, and assessed the association with socioeconomic and food consumption factors. We collected socioeconomic and food consumption data for 307 HIV positive antiretroviral naive adults and examined AF-ALB levels at recruitment (baseline) and at six (follow-up 1) and 12 (follow-up 2) months post-recruitment, by age, gender, socioeconomic status (SES) and food consumption patterns. Generalized linear models were used to examine the influence of socioeconomic and food consumption factors on changes in AF-ALB levels over the study period, adjusting for other covariates. AF-ALB levels (pg/mg albumin) were lower at baseline (mean AF-ALB: 14.9, SD: 15.9), higher at six months (mean AF-ALB: 23.3, SD: 26.6), and lower at 12 months (mean AF-ALB: 15.3, SD: 15.4). Participants with the lowest SES had the highest AF-ALB levels at baseline and follow up-2 compared with those with higher SES. Participants who bought less than 20% of their food and who stored maize for less than two months had lower AF-ALB levels. In the adjusted models, there was a statistically significant association between follow up time and season (dry or rainy season) on AF-ALB levels over time (p = 0.04). Asymptomatic HIV-positive Ghanaians had high plasma AF-ALB levels that varied according to season, socioeconomic status, and food consumption patterns. Steps need to be taken to ensure the safety and security of the food supply for the population, but in particular for the most vulnerable groups such as HIV positive people. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Open AccessArticle

Metabolic and Hematological Consequences of Dietary Deoxynivalenol Interacting with Systemic Escherichia coli Lipopolysaccharide

by Erik Bannert, Tanja Tesch, Jeannette Kluess, Jana Frahm, Susanne Kersten, Stefan Kahlert, Lydia Renner, Hermann-Josef Rothkötter and Sven Dänicke

Toxins 2015, 7(11), 4773-4796; https://doi.org/10.3390/toxins7114773 - 16 Nov 2015

Cited by 21 | Viewed by 4904

Abstract

Previous studies have shown that chronic oral deoxynivalenol (DON) exposure modulated Escherichia coli lipopolysaccharide (LPS)-induced systemic inflammation, whereby the liver was suspected to play an important role. Thus, a total of 41 barrows was fed one of two maize-based diets, either a DON-diet (4.59 mg DON/kg feed, n = 19) or a control diet (CON, n = 22). Pigs were equipped with indwelling catheters for pre- or post-hepatic (portal vs. jugular catheter) infusion of either control (0.9% NaCl) or LPS (7.5 µg/kg BW) for 1h and frequent blood sampling. This design yielded six groups: CON_CON_jugular‑CON_portal, CON_CON_jugular‑LPS_portal, CON_LPS_jugular‑CON_portal, DON_CON_jugular‑CON_portal, DON_CON_jugular‑LPS_portal and DON_LPS_jugular‑CON_portal. Blood samples were analyzed for blood gases, electrolytes, glucose, pH, lactate and red hemogram. The red hemogram and electrolytes were not affected by DON and LPS. DON-feeding solely decreased portal glucose uptake (p < 0.05). LPS-decreased partial oxygen pressure (pO₂) overall (p < 0.05), but reduced pCO₂ only in arterial blood, and DON had no effect on either. Irrespective of catheter localization, LPS decreased pH and base-excess (p < 0.01), but increased lactate and anion-gap (p < 0.01), indicating an emerging lactic acidosis. Lactic acidosis was more pronounced in the group DON_LPS_jugular-CON_portal than in CON-fed counterparts (p < 0.05). DON-feeding aggravated the porcine acid-base balance in response to a subsequent immunostimulus dependent on its exposure site (pre- or post-hepatic). Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Open AccessArticle

The Effects of Low Doses of Two Fusarium Toxins, Zearalenone and Deoxynivalenol, on the Pig Jejunum. A Light and Electron Microscopic Study

by Barbara Przybylska-Gornowicz, Michał Tarasiuk, Bogdan Lewczuk, Magdalena Prusik, Natalia Ziółkowska, Łukasz Zielonka, Maciej Gajęcki and Magdalena Gajęcka

Toxins 2015, 7(11), 4684-4705; https://doi.org/10.3390/toxins7114684 - 11 Nov 2015

Cited by 44 | Viewed by 6548

Abstract

Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin

by Rong Yang, Yi-Mei Wang, Li-Shi Zhang, Li Zhang, Zeng-Ming Zhao, Jun Zhao and Shuang-Qing Peng

Toxins 2015, 7(11), 4668-4683; https://doi.org/10.3390/toxins7114668 - 9 Nov 2015

Cited by 18 | Viewed by 6601

Abstract

Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

by Erica S. Clark, Brenna M. Flannery, Elizabeth M. Gardner and James J. Pestka

Toxins 2015, 7(10), 4199-4215; https://doi.org/10.3390/toxins7104199 - 19 Oct 2015

Cited by 20 | Viewed by 5569

Abstract

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Risk Assessment on Dietary Exposure to Aflatoxin B₁ in Post-Harvest Peanuts in the Yangtze River Ecological Region

by Xiaoxia Ding, Linxia Wu, Peiwu Li, Zhaowei Zhang, Haiyan Zhou, Yizhen Bai, Xiaomei Chen and Jun Jiang

Toxins 2015, 7(10), 4157-4174; https://doi.org/10.3390/toxins7104157 - 15 Oct 2015

Cited by 41 | Viewed by 7146

Abstract

Based on the 2983 peanut samples from 122 counties in six provinces of China’s Yangtze River ecological region collected between 2009–2014, along with the dietary consumption data in Chinese resident nutrition and health survey reports from 2002 and 2004, dietary aflatoxin exposure and percentiles in the corresponding statistics were calculated by non-parametric probability assessment, Monte Carlo simulation and bootstrap sampling methods. Average climatic conditions in the Yangtze River ecological region were calculated based on the data from 118 weather stations via the Thiessen polygon method. The survey results found that the aflatoxin contamination of peanuts was significantly high in 2013. The determination coefficient (R²) of multiple regression reflected by the aflatoxin B₁ content with average precipitation and mean temperature in different periods showed that climatic conditions one month before harvest had the strongest impact on aflatoxin B₁ contamination, and that Hunan and Jiangxi provinces were greatly influenced. The simulated mean aflatoxin B₁ intake from peanuts at the mean peanut consumption level was 0.777–0.790 and 0.343–0.349 ng/(kg·d) for children aged 2–6 and standard adults respectively. Moreover, the evaluated cancer risks were 0.024 and 0.011/(100,000 persons·year) respectively, generally less than China’s current liver cancer incidence of 24.6 cases/(100,000 persons·year). In general, the dietary risk caused by peanut production and harvest was low. Further studies would focus on the impacts of peanut circulation and storage on aflatoxin B₁ contamination risk assessment in order to protect peanut consumers’ safety and boost international trade. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Deoxynivalenol Exposure Assessment for Pregnant Women in Bangladesh

by Nurshad Ali, Meinolf Blaszkewicz, Abdullah Al Nahid, Mustafizur Rahman and Gisela H. Degen

Toxins 2015, 7(10), 3845-3857; https://doi.org/10.3390/toxins7103845 - 24 Sep 2015

Cited by 34 | Viewed by 5178

Abstract

The trichothecene mycotoxin deoxynivalenol (DON) is a contaminant of crops worldwide and known to cause adverse health effects in exposed animals and humans. A small survey reported the presence of DON in maize samples in Bangladesh, but these data are insufficient to assess human exposure, and also, biomonitoring data are still scarce. The present study applied biomarker analysis to investigate the DON exposure of pregnant women in Bangladesh. Urine samples were collected from pregnant women living in a rural (n = 32) and in a suburban (n = 22) area of the country. Urines were subjected to enzymatic hydrolysis of glucuronic acid conjugates and to immunoaffinity column clean-up prior to LC-MS/MS analysis of DON and its de-epoxy metabolite DOM-1. The limits of detection (LOD) for DON and DOM-1 in urine were 0.16 ng/mL and 0.10 ng/mL, respectively. DOM-1 was not detected in any of the urines, whilst DON was detectable in 52% of the samples at levels ranging from 0.18–7.16 ng/mL and a mean DON concentration of 0.86 ± 1.57 ng/mL or 2.14 ± 4.74 ng/mg creatinine. A significant difference in mean urinary DON levels was found between the rural (0.47 ± 0.73 ng/mL) and suburban (1.44 ± 2.20 ng/mL) cohort, which may be related to different food habits in the two cohorts. Analysis of food consumption data for the participants did not show significant correlations between their intake of typical staple foods and DON levels in urine. The biomarker concentrations found and published urinary excretion rates for DON were used to estimate daily mycotoxin intake in the cohort: the mean DON intake was 0.05 µg/kg b.w., and the maximum intake was 0.46 µg/kg b.w., values lower than the tolerable daily intake of 1 µg/kg b.w. These first results indicate a low dietary exposure of pregnant women in Bangladesh to DON. Nonetheless, further biomonitoring studies in children and in adult cohorts from other parts of the country are of interest to gain more insight into DON exposure in the population of Bangladesh. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Open AccessArticle

Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

by Paola Giorni, Chiara Dall'Asta, Massimo Reverberi, Valeria Scala, Matteo Ludovici, Martina Cirlini, Gianni Galaverna, Corrado Fanelli and Paola Battilani

Toxins 2015, 7(9), 3657-3670; https://doi.org/10.3390/toxins7093657 - 11 Sep 2015

Cited by 9 | Viewed by 5174

Abstract

Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Murine Anorectic Response to Deoxynivalenol (Vomitoxin) Is Sex-Dependent

by Erica S. Clark, Brenna M. Flannery and James J. Pestka

Toxins 2015, 7(8), 2845-2859; https://doi.org/10.3390/toxins7082845 - 29 Jul 2015

Cited by 17 | Viewed by 5972

Abstract

Deoxynivalenol (DON, vomitoxin), a common trichothecene mycotoxin found in cereal foods, dysregulates immune function and maintenance of energy balance. The purpose of this study was to determine if sex differences are similarly evident in DON’s anorectic responses in mice. A bioassay for feed refusal, previously developed by our lab, was used to compare acute i.p. exposures of 1 and 5 mg/kg bw DON in C57BL6 mice. Greater anorectic responses were seen in male than female mice. Male mice had higher organ and plasma concentrations of DON upon acute exposure than their female counterparts. A significant increase in IL-6 plasma levels was also observed in males while cholecystokinin response was higher in females. When effects of sex on food intake and body weight changes were compared after subchronic dietary exposure to 1, 2.5, and 10 ppm DON, males were found again to be more sensitive. Demonstration of male predilection to DON-induced changes in food intake and weight gain might an important consideration in future risk assessment of DON and other trichothecenes. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Prevention of Aflatoxin B₁-Induced DNA Breaks by β-D-Glucan

by Eduardo Madrigal-Bujaidar, José Antonio Morales-González, Manuel Sánchez-Gutiérrez, Jeannett A. Izquierdo-Vega, Alicia Reyes-Arellano, Isela Álvarez-González, Ricardo Pérez-Pasten and Eduardo Madrigal-Santillán

Toxins 2015, 7(6), 2145-2158; https://doi.org/10.3390/toxins7062145 - 11 Jun 2015

Cited by 21 | Viewed by 5454

Abstract

Aflatoxins are a group of naturally-occurring carcinogens that are known to contaminate different human and animal foodstuffs. Aflatoxin B₁ (AFB₁) is the most genotoxic hepatocarcinogenic compound of all of the aflatoxins. In this report, we explore the capacity of β-D-glucan (Glu) to reduce the DNA damage induced by AFB₁ in mouse hepatocytes. For this purpose, we applied the comet assay to groups of animals that were first administered Glu in three doses (100, 400 and 700 mg/kg bw, respectively) and, 20 min later, 1.0 mg/kg of AFB₁. Liver cells were obtained at 4, 10 and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB₁ with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The data suggested the formation of a supramolecular complex between AFB₁ and β-D-glucan. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

by Seong-Hwan Park, Dongwook Kim, Juil Kim and Yuseok Moon

Toxins 2015, 7(11), 4484-4502; https://doi.org/10.3390/toxins7114484 - 30 Oct 2015

Cited by 20 | Viewed by 6577

Abstract

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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A Novel Peptide-Binding Motifs Inference Approach to Understand Deoxynivalenol Molecular Toxicity

by Yousef I. Hassan, Christena Watts, Xiu-Zhen Li and Ting Zhou

Toxins 2015, 7(6), 1989-2005; https://doi.org/10.3390/toxins7061989 - 2 Jun 2015

Cited by 30 | Viewed by 6771

Abstract

Deoxynivalenol (DON) is a type B trichothecene mycotoxin that is commonly detected in cereals and grains world-wide. The low-tolerated levels of this mycotoxin, especially in mono-gastric animals, reflect its bio-potency. The toxicity of DON is conventionally attributed to its ability to inhibit ribosomal protein biosynthesis, but recent advances in molecular tools have elucidated novel mechanisms that further explain DON’s toxicological profile, complementing the diverse symptoms associated with its exposure. This article summarizes the recent findings related to novel mechanisms of DON toxicity as well as how structural modifications to DON alter its potency. In addition, it explores feasible ways of expanding our understating of DON-cellular targets and their roles in DON toxicity, clearance, and detoxification through the utilization of computational biology approaches. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)

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