Deoxynivalenol Impairs Weight Gain and Affects Markers of Gut Health after Low-Dose, Short-Term Exposure of Growing Pigs

Alizadeh, Abolfath; Braber, Saskia; Akbari, Peyman; Garssen, Johan; Fink‐Gremmels, Johanna

doi:10.3390/toxins7062071

Cited by 92 publications

(73 citation statements)

References 72 publications

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“…Deng (Deng et al, 2015) investigated the distribution of DON in plasma, bile and 27 tissues after i.v. The same conclusions were reached by Alizadeh (Alizadeh et al, 2015), who measured the effects of a short-term and comparable DON exposure (0.28 mg/kg bw) on various gut health parameters in pigs. The same conclusions were reached by Alizadeh (Alizadeh et al, 2015), who measured the effects of a short-term and comparable DON exposure (0.28 mg/kg bw) on various gut health parameters in pigs.…”

Section: Ochratoxin Asupporting

confidence: 71%

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Battilani¹,

Palumbo²,

Giorni³

et al. 2020

EFS3

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Mycotoxins are toxic compounds mainly produced by fungi of the genera Aspergillus, Penicillium and Fusarium. They are present, often as mixtures, in many feed and food commodities including cereals, fruits and vegetables. Their ubiquitous presence represents a major challenge to the health and well being of humans and animals. Hundreds of compounds are listed as possible mycotoxins occurring in raw and processed materials destined for human food and animal feed. In this study, mycotoxins of major toxicological relevance to humans and target animal species were investigated in a range of crops of interest (and their derived products). Extensive Literature Searches (ELSs) were undertaken for data collection on: (i) ecology and interaction with host plants of mycotoxin producing fungi, mycotoxin production, recent developments in mitigation actions of mycotoxins in crop chains (maize, small grains, rice, sorghum, grapes, spices and nuts), (ii) analytical methods for native, modified and co-occurring mycotoxins (iii) toxicity, toxicokinetics, toxicodynamics and biomarkers relevant to humans and animals (poultry, suidae (pig, wild boar), bovidae (sheep, goat, cow, buffalo), rodents (rats, mice) and others (horses, dogs), (iv) modelling approaches and key reference values for exposure, hazard and risk modelling. Comprehensive databases were created using EFSA templates and were stored in the MYCHIF platform. A range of approaches were implemented to explore the modelling of external and internal exposure as well as dose-response of mycotoxins in chicken and pigs. In vitro toxicokinetic and in vivo toxicity databases were exploited, both for single compounds and mixtures. However, large data gaps were identified particularly with regards to absence of common statistical and study designs within the literature and constitute an obstacle for the harmonisation of internal exposure and dose-response modelling. Finally, risk characterisation was also performed for humans as well as for two animal species (i.e. pigs and chicken) using available tools for the modelling of internal dose and a component-based approach for selected mycotoxins mixtures.© European Food Safety Authority, 2020 MYCHIF www.efsa.europa.eu/publications 2 EFSA Supporting publication 2020: EN-1757

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Section: Ochratoxin Asupporting

confidence: 71%

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Battilani¹,

Palumbo²,

Giorni³

et al. 2020

EFS3

View full text Add to dashboard Cite

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“…We also observe the interference of DON with genes involved in other biological functions such as oxidative stress, cell cycle molecular transport and mitochondrial functions. As recently described in vivo (Alizadeh et al 2015), a decreased expression of mRNA levels of efflux transporters was also observed in intestinal explants exposed to DON. Studies reported that DON is a substrate for ABC transporter (Videmann et al 2007); thus, a decrease expression of efflux protein would decrease uptake of DON by intestinal cells and therefore decrease its toxicity.…”

Section: Figsupporting

confidence: 52%

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

et al. 2015

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Natural food contaminants such as mycotoxins are an important problem for human health. Deoxynivalenol (DON) is one of the most common mycotoxins detected in cereals and grains. Its toxicological effects mainly concern the immune system and the gastrointestinal tract. This toxin is a potent ribotoxic stressor leading to MAP kinase activation and inflammatory response. DON frequently co-occurs with its glucosylated form, the masked mycotoxin deoxynivalenol-3-β-D-glucoside (D3G). The toxicity of this later compound remains unknown in mammals. This study aimed to assess the ability of D3G to elicit a ribotoxic stress and to induce intestinal toxicity. The toxicity of D3G and DON (0-10 µM) was studied in vitro, on the human intestinal Caco-2 cell line, and ex vivo, on porcine jejunal explants. First, an in silico analysis revealed that D3G, contrary to DON, was unable to bind to the A-site of the ribosome peptidyl transferase center, the main targets for DON toxicity. Accordingly, D3G did not activate JNK and P38 MAPKs in treated Caco-2 cells and did not alter viability and barrier function on cells, as measured by the trans-epithelial electrical resistance. Treatment of intestinal explants for 4 h with 10 µM DON induced morphological lesions and up-regulated the expression of pro-inflammatory cytokines as measured by qPCR and pan-genomic microarray analysis. By contrast, expression profile of D3G-treated explants was similar to that of controls, and these explants did not show histomorphology alteration. In conclusion, our data demonstrated that glucosylation of DON suppresses its ability to bind to the ribosome and decreases its intestinal toxicity.

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“…Especially, IL-22 in the gut is able to stimulate intestinal epithelial cells to produce antimicrobial peptides, enhance the intestinal epithelial barrier of mucus and promote intestinal repair (Hou et al, 2018;Parks et al, 2015). Pathogens such as enterotoxigenic Escherichia coli (ETEC) and mycotoxin in contaminated feed are destructive to intestinal epithelial cells, which cause enteritis and seriously threatens gut health of pigs (Alizadeh et al, 2015;Lee et al, 2016;Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Protecting intestinal epithelial cells against deoxynivalenol and E. coli damage by recombinant porcine IL-22

Wang

et al. 2019

Veterinary Microbiology

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Pigs suffer enteritis induced by pathogenic bacteria infection and toxins in the moldy feed, which cause intestinal epithelial damage and diarrhea through the whole breeding cycle. Interleukin-22 (IL-22) plays a critical role in maintaining intestinal mucosal barrier function through repairing intestinal epithelial damage. However, little was known about the effects of IL-22 against apoptosis caused by toxins and infection of intestinal pathogens in the intestinal epithelium, especially in pigs. In this study, we had successfully used prokaryotic expression system to produce recombinant porcine interleukin-22. Meanwhile, purified rIL-22 could activate STAT3 signal pathway and have been demonstrated to be safe to IPEC-J2 cells by increasing E-cadherin expression, without proinflammatory cytokines changes. Furthermore, rIL-22 reversed apoptosis induced by deoxynivalenol (DON) and played a vital part in repairing the intestinal injury. We also found that rIL-22 stimulated epithelial cells to secrete pBD-1 against enterotoxigenic E. coli (ETEC) K88 infection, as well as alleviating apoptosis ratio. This study provided a theoretical basis for curing intestinal inflammation caused by ETEC infection and epithelial apoptosis induced by DON with rIL-22 in pigs.

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Deoxynivalenol Impairs Weight Gain and Affects Markers of Gut Health after Low-Dose, Short-Term Exposure of Growing Pigs

Cited by 92 publications

References 72 publications

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

Protecting intestinal epithelial cells against deoxynivalenol and E. coli damage by recombinant porcine IL-22

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