Background
Mycotoxins are metabolites of fungi that are harmful to humans and animals and are often found in feed and food. Deoxynivalenol (DON) is a fungal toxin associated with Fusarium head blight and can be produced by Fusarium spp. DON was first extracted from moldy wheat and corn by Japanese scholars and chemically identified, it belongs to class B trichothecene compounds. DON is soluble in water, ethanol, ethyl acetate, and other solvents, and is stable under pressure, heat, and in acidic environments, but its toxicity decreases in alkaline environments. DON is very stable and can be present in contaminated wheat stored for up to 4 years. DON contaminants are mainly contaminated in crops such as maize, wheat, barley and potatoes, and can also be isolated from cereal products such as beer and soy sauce, and animal products such as meat, eggs and milk. Due to the large economic losses caused by DON, the Food and Agriculture Organization and the World Health Organization have identified DON as one of the most dangerous natural food contaminants.
Figure 1. Structural formula of DON
(Source: Yao Y, et al. 2020)
DON is named vomitoxin because of the vomiting that occurs when animals consume contaminated feed. Animals usually exhibit anorexia, nausea, vomiting and diarrhea after DON poisoning, and their immune and reproductive functions are also affected. DON toxicity in humans is manifested by stomach upset, vomiting, dizziness, headache, abdominal pain, and diarrhea. DON is metabolized in the body and binds to ribosomes, thereby destroying the structure of the ribosomes. Studies have shown that DON also interferes with the active center of peptidyl transferase on the 60S subunit of the ribosome, thereby inhibiting normal protein synthesis. It also activates the MAPK signaling pathway, which causes various physiological responses.
DON toxicity can be detoxified by physical, chemical and biological methods. Physical detoxification involves the use of physical methods to reduce the concentration of DON, such as heat treatment, washing and grinding, and adsorption. Chemical detoxification mainly uses strong oxidants (such as strong acids, bases, or ozone) to treat DON contaminated grains. This process converts DON into a substance that is low or even completely non-toxic. Biological detoxification is treated by using microorganisms to adsorb toxic substances or produce enzymes that degrade toxins. This method has mild reaction conditions and good detoxification effect, and is considered superior to physical and chemical detoxification methods.
Alternative Names
anti-DON monoclonal antibody
References
- 1. Yao Y, et al. The biological detoxification of deoxynivalenol: A review. Food Chem Toxicol. 2020 Nov;145:111649.
- 2. Li Y, et al. Deoxynivalenol in food and feed: Recent advances in decontamination strategies. Front Microbiol. 2023 Mar 14;14:1141378.
References
Quercetin Alleviates Deoxynivalenol-Induced Intestinal Damage by Suppressing Inflammation and Ferroptosis in Mice
J Agric Food Chem
Authors: Ye Y, Jiang M, Hong X, Fu Y, Chen Y, Wu H, Sun Y, Wang X, Zhou E, Wang J, Yang Z.
Abstract
Deoxynivalenol (DON), one of the most prevalent mycotoxins found in food and feed, can cause gastrointestinal inflammation and systemic immunosuppression, presenting a serious hazard to human and animal health. Quercetin (QUE) is a plant polyphenol with anti-inflammatory and antioxidant properties. In this research, we investigated the potential function of QUE as a treatment for DON-induced intestinal damage. Thirty male specific-pathogen-free BALB/c mice were randomly allocated to treatment with QUE (50 mg/kg) and/or DON (0, 0.5, 1, and 2 mg/kg). We found that QUE attenuated DON-induced intestinal damage in mice by improving jejunal structural injury and changing tight junction proteins (claudin-1, claudin-3, ZO-1, and occludin) levels. QUE also suppressed DON-triggered intestinal inflammation by inhibiting the TLR4/NF-κB signaling pathway. Meanwhile, QUE decreased the oxidative stress caused by DON by enhancing the concentrations of SOD and GSH, while diminishing the contents of MDA. In particular, QUE reduced DON-induced intestinal ferroptosis. DON-induced intestinal damage elevated TfR and 4HNE levels, along with transcription levels of ferroptosis-related genes (PTGS2, ACSL4, and HAMP1) while diminishing mRNA levels of FTH1, SLC7A11, GPX4, FPN1, and FSP1, all of which were reversed by QUE treatment. Our findings imply that QUE alleviates DON-induced intestinal injury in mice by inhibiting the TLR4/NF-κB signaling pathway and ferroptosis. In this study, we elucidate the toxicological mechanism of DON, provide a basic foundation or theory for future DON prevention and treatment, and explore strategies to prevent and alleviate DON's hazardous effects.
Resveratrol protects against deoxynivalenol-induced ferroptosis in HepG2 cells
Toxicology
Authors: Wang P, Yao Q, Zhu D, Yang X, Chen Q, Lu Q, Liu A.
Abstract
Deoxynivalenol (DON) is one of the most serious mycotoxins that contaminate food and feed, causing hepatocyte death. However, there is still a lack of understanding regarding the new cell death modalities that explain DON-induced hepatocyte toxicity. Ferroptosis is an iron-dependent type of cell death. The aim of this study was to explore the role of ferroptosis in DON-exposed HepG2 cytotoxicity and the antagonistic effect of resveratrol (Res) on its toxicity, and the underlying molecular mechanisms. HepG2 cells were treated with Res (8 μM) or/and DON (0.4 μM) for 12 h. We examined cell viability, cell proliferation, expression of ferroptosis-related genes, levels of lipid peroxidation and Fe(II). The results revealed that DON reduced the expression levels of GPX4, SLC7A11, GCLC, NQO1, and Nrf2 while promoting the expression of TFR1, GSH depletion, accumulation of MDA and total ROS. DON enhanced production of 4-HNE, lipid ROS and Fe(II) overload, resulting in ferroptosis. However, pretreatment with Res reversed these changes, attenuating DON-induced ferroptosis, improving cell viability and cell proliferation. Importantly, Res prevented Erastin and RSL3-induced ferroptosis, suggesting that Res exerted an anti-ferroptosis effect by activating SLC7A11-GSH-GPX4 signaling pathways. In summary, Res ameliorated DON-induced ferroptosis in HepG2 cells. This study provides a new perspective on the mechanism of DON-induced hepatotoxicity formation, and Res may be an effective drug to alleviate DON-induced hepatotoxicity.
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