Deoxynivalenol Toxicity Research Articles

Efficacy of High-Dose Synbiotic Additives for Deoxynivalenol Detoxification: Effects on Blood Biochemistry, Histology, and Intestinal Microbiome in Weaned Piglets.

Deoxynivalenol (DON) is a common mycotoxin observed in cereal grains, and feed contamination poses health risks to pigs. Biological antidotes, such as synbiotics (SYNs), have garnered attention for mitigating DON toxicity. This study aimed to assess the efficacy of SYNs by comparing the blood biochemistry, histology, and gut microbiome of weaned piglets. A 4-week trial was conducted on 32 weaned piglets. After a week of diet and environmental adaptation, the pigs were divided into four groups: (1) control (CON, n = 8); (2) SYN (n = 8); (3) DON (n = 8); and (4) DON+SYN (n = 8). The SYN supplementation of weaned piglets increased the final body weight (21.71 ± 0.93 vs. 20.73 ± 0.84), average daily gain (0.38 ± 0.02 vs. 0.34 ± 0.02), and gain-to-feed ratio (0.49 ± 0.04 vs. 0.43 ± 0.02), and decreased the feed conversion ratio (2.14 ± 0.14 vs. 2.39 ± 0.13) compared to the DON group. A high dose of DON induced liver and colon fibrosis and liver and cecum apoptosis, which were alleviated by SYNs. Glucose in the DON group (84.9 ± 3.7) was significantly lower than in the control (101.3 ± 4.2). Additionally, both the DON and DON+SYN groups exhibited higher creatine (0.9 ± 0.0 and 0.9 ± 0.1) and lower cholesterol (88.3 ± 3.2 and 90.0 ± 4.8) levels (p < 0.05). In conclusion, SYNs alleviated DON toxicity, indicating its potential as an antidote for specific biomarkers.

Deoxynivalenol induces ovarian damage and uterine changes in prepubertal and adult mice

Deoxynivalenol (DON) is associated with reproductive toxicity in animals. The frequent contamination of cereal-based foods with DON and the high intake of these by children raises particular concern about the susceptibility of this subpopulation to adverse effects from this mycotoxin. However, age-related differences in the in vivo reproductive toxicity of DON have not been evaluated. Therefore, the effects of DON on serum follicle-stimulating hormone (FSH) levels, histology, and inflammatory and oxidative stress responses in the ovaries and uteruses of prepubertal and adult mice were investigated. Twenty female prepubertal Swiss mice (21 days old) and 20 young adult mice (65 days old) were fed a control diet or a diet containing 10 mg of DON/kg of feed for 15 days (prepubertal mice) and 28 days (adult mice). In the ovaries, DON induced an increase in the lesional score in both age groups. Ingestion of DON decreased FSH levels in prepubertal females, whereas an increase was observed in adult mice. In prepubertal mice, a reduction in the number of macrophages and increased levels of TNF-α were observed in the ovaries of the DON group, while in adult animals, an increase in the number of macrophages and higher levels of TNF-α were noted. Exposure to DON led to an increase in type I collagen in the uteruses of adult mice, while in prepubertal mice, a decrease in type III collagen was observed. DON exposure also resulted in a decrease in FRAP levels and an increase in ABTS and lipid peroxidation in the uteruses of prepubertal mice. Taken together, the results indicate that the effects of DON on reproductive organs are age-specific, with toxicity established as early as the prepubertal period.

Deoxynivalenol-Induced Spleen Toxicity in Mice: Inflammation, Endoplasmic Reticulum Stress, Macrophage Polarization, and the Dysregulation of LncRNA Expression.

The spleen is a primary target of deoxynivalenol (DON) toxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of DON on inflammation, splenic macrophage polarization, endoplasmic reticulum (ER) stress, and transcriptome changes (mRNA and lncRNAs) in mouse spleen. We found that DON exposure at doses of 2.5 or 5 mg/kg BW significantly induced inflammation and polarized splenic macrophages towards the M1 phenotype. Additionally, DON activated PERK-eIF2α-ATF4-mediated ER stress and upregulated apoptosis-related proteins (caspase-12, caspase-3). The ER stress inhibitor, 4-Phenylbutyric acid, significantly alleviated DON-induced ER stress, apoptosis, and the M1 polarization of splenic macrophages. Transcriptome analysis identified 1968 differentially expressed (DE) lncRNAs and 2664 DE mRNAs in mouse spleen following DON exposure. Functional enrichment analysis indicated that the upregulated genes were involved in pathways associated with immunity, including Th17 cell differentiation, TNF signaling, and IL-17 signaling, while downregulated mRNAs were linked to cell survival and growth pathways. Furthermore, 370 DE lncRNAs were predicted to target 255 DE target genes associated with immune processes, including the innate immune response, interferon-beta response, cytokine production regulation, leukocyte apoptosis, and NF-κB signaling genes. This study provides new insights into the mechanisms underlying DON toxicity and its effects on the immune system.

Macrophage MAPK7/AhR/STAT3 Signaling Mediates Mitochondrial ROS Burst and Enterohepatic Inflammatory Responses Induced by Deoxynivalenol Relevant to Low-Dose Exposure in Children.

Deoxynivalenol (DON) can induce endoplasmic reticulum (ER) stress, mitochondrial ROS burst, and macrophage polarization. Here, we investigated the mechanism linking the above three aspects with the dose range relevant to low-level exposure in children. At 0.5 μg/kg bw/day, we found remarkable liver and gut inflammatory responses after 6-week exposure in mice age comparable to humans 7-12 years old. Through antioxidant intervention, we found that ROS played a driver role in macrophage polarization and inflammatory responses induced by DON in the liver and gut. Further bioinformatics analysis uncovered that ER stress-associated protein MAPK7 (ERK5) may bind with AhR to initiate a mitochondrial ROS burst and macrophage M1 polarization. The downstream cellular events of MAPK7-AhR interaction may be mediated by the AhR/STAT3/p-STAT(Ser727) pathway. This mechanism was further supported by DON toxicity mitigation using cyanidin-3-glucoside (C-3-G), which docks to MAPK7 oligomerization region 200-400 aa and disrupts MAPK7-AhR interaction. Overall, our study provides novel evidence and mechanism for DON-induced inflammatory responses in the liver and gut system. Our findings call attention to the health risks associated with low-level DON exposure in the prepuberty children population.

An fusaric acid-based CRISPR library screen identifies MDH2 as a broad-spectrum regulator of Fusarium toxin-induced cell death

Fusarium mycotoxins are of great concern because they are the most common food-borne mycotoxins and environmental contaminants worldwide. Fusaric acid (FA), Deoxynivalenol (DON), Zearalenone (ZEA), T-2 toxin (T-2), and Fumonisin B1 (FB1) are important Fusarium toxins contaminating feeds and food and can cause serious health problems. FA can synergize with some other Fusarium toxins to enhance overall toxicity. However, the underlying molecular mechanism remains poorly understood. In this study, our CRISPR screening revealed Malate dehydrogenase 2 (MDH2) and Pyruvate dehydrogenase E1 subunit beta (PDHB) are the key genes for FA-induced cell death. Pathways associated with mitochondrial function, notably the TCA cycle, play a significant role in FA cytotoxicity. We found that MDH2 and PDHB depletion reduced FA-induced cell death, ROS accumulation, and the expression of caspase-3 and HIF-1α. The cell viability assays and flow cytometry demonstrated that MDH2 knockout but not PDHB decreased DON, ZEA, T-2, and FB1-induced cytotoxicity, apoptosis, and ROS accumulation. MDH2 inhibitor LW6 also decreased DON, ZEA, T-2, and FB1-induced toxicity. This suggested that MDH2, but not PDHB, is a common regulator of broad-spectrum Fusarium toxin (FA, DON, ZEA, T-2, and FB1)-induced cell death. Our work provides new avenues for the treatment of Fusarium toxin toxicity.

Low concentrations of the food contaminant Deoxynivalenol trigger apoptosis and impair GnRH-induced LH secretion in pituitary gonadotrope-like cells.

AbstractTheFusariummycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. Nearly all individuals are exposed to DON, due to it widespread presence in grains and grain-based products. Chronic DON poisoning is associated with growth retardation, immunotoxicity as well as impaired reproduction and fetal development. At the molecular level, DON alters intracellular signaling by activating mitogen-activated protein kinases (MAPKs) that modulate cell growth, differentiation, and apoptosis. Of note, these MAPKs are also critical mediators of gonadotrophin-releasing hormone (GnRH)-induced synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotrope cells. So far, no research has explored the potential endocrine-disrupting effects of DON on pituitary gonadotropins production. Herein, we show the first evidence that DON affects LH production by the immortalized gonadotrope-like cell line LβT2 in a concentration-dependent manner. Taken together, our experiments demonstrated that low concentrations of DON affect GnRH-induced signaling through a mechanism that, at least in part, involves apoptosis and inhibition of GnRH-induced phosphorylation of ERK-MAPK. Consequently, DON also affects the GnRH-induced expression ofCgaandLhb, two critical genes for LH synthesis and secretion by gonadotrope cells in mammals. This research broadens our knowledge of the toxicity of DON and brings a new depth to the potential neuroendocrine implications for reproduction.Graphical abstract

Unexpected antagonism of deoxynivalenol and enniatins in intestinal toxicity through the Ras/PI3K/AKT signaling pathway

Deoxynivalenol (DON) is a kind of widespread traditional Fusarium mycotoxins in the environment, and its intestinal toxicity has received considerable attention. Recently, the emerging Fusarium mycotoxin enniatins (ENNs) have also been shown to frequently coexist with DON in animal feed and food with large consumption. However, the mechanism of intestinal damage caused by the two mycotoxins co-exposure remains unclear. In this study, Caco-2 cell line was used to investigate the combined toxicity and potential mechanisms of four representative ENNs (ENA, ENA1, ENB, and ENB1) and DON. The results showed that almost all mixed groups showed antagonistic effects, particularly ENB at 1/4 IC50 (CI = 6.488). Co-incubation of ENNs mitigated the levels of signaling molecule levels disrupted by DON, including reactive oxygen species (ROS), calcium mobilization (Ca2+), adenosine triphosphate (ATP). The differentially expressed genes (DEGs) between the mixed and ENB groups were significantly enriched in the Ras/PI3K/Akt signaling pathway, including 28 up-regulated genes and 40 down-regulated genes. Quantitative real-time PCR further confirmed the lower expression of apoptotic gene in the mixed group, thereby reducing the cytotoxic effects caused by DON exposure. This study emphasizes that co-exposure of ENNs and DON reduces cytotoxicity by regulating the Ras/PI3K/Akt signaling pathway. Our results provide the first comprehensive evidence about the antagonistic toxicity of ENNs and DON on Caco-2 cells, and new insights into mechanisms investigated by transcriptomics.

Acute toxicity of deoxynivalenol and bioremediation of a highly effective deoxynivalenol degrading Achromobacter spanius P-9 on zebrafish embryos and adults

Deoxynivalenol (DON) is one of the mostly concerned mycotoxins and several microbes showed bioremediation effects on DON toxic effects. In this study, the acute toxicity of a new DON degrading strain Achromobacter spanius P-9 with DON on zebrafish embryos and adults were firstly performed. For zebrafish embryos, bacterial concentrations of 2.5 × 107 CFU/mL and 5.0 × 107 CFU/mL had no significant effects on growth and development. However, at 7.5 × 107 CFU/mL, some effects were observed, and at 10.0 × 107 CFU/mL, the embryo survival rate decreased to 70%, with 3.3% teratogenicity. Higher bacterial concentrations correlated with faster heart rates. DON (100 μg/mL) significantly reduced embryo survival to 36.7% in 96 h. Bacterial solutions at 7.5 × 107 CFU/mL and 10.0 × 107 CFU/mL expanded the zebrafish intestinal tissue wall, while DON at 100 μg/mL negatively impacted intestinal morphology. Liver tissue in zebrafish exposed to Achromobacter spanius P-9 showed no significant differences from the control group. However, exposure to DON solution increased liver fluorescence intensity and caused liver cell changes, including edema, vacuolization, and blurred boundaries. For adult zebrafish, the ROS and 8-OHdG contents in the exposure group increased with the increase of bacterial solution concentration, the SOD enzyme activity, CAT enzyme activity, GST enzyme activity and MDA was not significantly different with the control group. Compared with the control group, the content of ROS, GST enzyme activity, MDA and 8-OHdG after DON treatment showed an upward trend, SOD and CAT enzyme activities showed a decreasing trend. Achromobacter spanius P-9 has no obvious inhibitory effect on the growth and development of zebrafish embryos and has no obvious death and toxicity during the growth of adult fish, providing data support for the future application of this strain in the biodegradation of DON.

Investigation of Deoxynivalenol Contamination in Local Area and Evaluation of Its Multiple Intestinal Toxicity.

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium fungi widespread in wheat, corn, barley and other grain crops, posing the potential for being toxic to human and animal health, especially in the small intestine, which is the primary target organ for defense against the invasion of toxins. This study firstly investigated DON contamination in a local area of a wheat production district in China. Subsequently, the mechanism of DON toxicity was analyzed through cellular molecular biology combining with intestinal flora and gene transcription analysis; the results indicated that DON exposure can decrease IPEC-J2 cell viability and antioxidant capacity, stimulate the secretion and expression of proinflammatory factors, destroy the gut microbiota and affect normal functions of the body. It is illustrated that DON could induce intestinal damage through structural damage, functional injury and even intestinal internal environment disturbance, and, also, these intestinal toxicity effects are intrinsically interrelated. This study may provide multifaceted information for the treatment of intestinal injury induced by DON.

Toxicity and metabolism of deoxynivalenol and its reversal by Bacillus subtilis in broiler chickens

The present study aimed to investigate the effect of Bacillus subtilis (B. subtilis) on the residue, metabolism, and biotransformation of deoxynivalenol (DON) in broiler chickens. There were 7 dietary treatments including a control and a factorial design with two factors, DON at 3 and 6 mg/kg and B. subtilis at 0, 106 and 109 CFU/kg of diet. A total of 420 broiler chickens at one day old were randomly distributed to 7 groups with 6 replicates of 10 chickens each. The feeding trial lasted for 21 days. Results showed that DON decreased and B. subtilis increased feed intake, body weight gain, and feed efficiency; and an interaction was found on feed intake. In the liver and ileal digesta, the two dietary factors conversely influenced the contents of DON residue and the metabolites (DON glucuronides and deepoxy-deoxynivalenol) of enzymes and microbe; and there was an interaction on deepoxy-deoxynivalenol. Also, in the liver and ileal mucosa, the activities of detoxifying enzymes (cytochrome P450, glutathione s-transferase α, epoxide hydrolase 1, and uridine diphosphate glucuronosyltransferase) and inflammatory factors (interleukin 1β, tumor necrosis factor α, interleukin 6, and interleukin-1 receptor antagonist) were conversely changed by the two dietary factors; and there were interactions on epoxide hydrolase 1, interleukin 1β, and tumor necrosis factor α. Additionally, B. subtilis at 109 CFU/kg showed greater effects on deepoxy-deoxynivalenol, epoxide hydrolase 1, and tumor necrosis factor α than that of 106 CFU/kg. It is concluded that the selected probiotics can decrease DON toxicity by microbial transformation and enzymatic metabolism in farm animals.

Application and efficacy of beidellite clay for the adsorption and detoxification of deoxynivalenol (vomitoxin)

The incidence of mycotoxin occurrence throughout the entire lifespan of some agricultural products could be due to climatic conditions and environmental factors (including high temperature, drought, and heavy rainfall) that enhance growth of fungi. Deoxynivalenol (DON) which is also referred to as vomitoxin is a mycotoxin produced from many Fusarium species. DON ranks high among the prominent mycotoxins in cereal products and is a ubiquitous toxin in livestock feeds. DON's adverse effects present major health challenges in both livestock and humans. The use of natural sorbents including smectite clays, is an economically feasible strategy to mitigate mycotoxin toxicities. Previous studies have demonstrated the potential of edible clays as protective components of human food and animal feed to alleviate toxicity associated with short-term exposure to mycotoxins including DON. Hence, this study was designed to investigate the sorption mechanisms of DON onto the binding surfaces of beidellite clay, assessing essential binding parameters such as enthalpy, free energy, binding capacity, affinity, and plateau surface density. These markers were used to predict availability of DON under the experimental conditions. Furthermore, the protection of beidellite clay against DON-induced toxicity was carried out using living organisms susceptible to DON toxicity, including Hydra vulgaris and Lemna minor. These studies investigated the dose-dependent detoxification of DON by 0.05–2 % inclusion of beidellite. Beidellite exhibited more than 75 % protection in Lemna minor and 53 % in Hydra vulgaris validating that this clay is effective in detoxifying DON. During emergencies, or after disasters, inclusion of edible clay like beidellite in food, water or capsules could reduce bioavailability of DON and halt potential exposures to humans and animals.

Mechanism of mitigating on Deoxynivalenol-induced intestinal toxicity in swine and its dietary regulation strategy1

Mycotoxins are the most widely present pollutants in both dietary provisions and livestock feed, and they pose a series of hazards for humans and animals. Deoxynivalenol (DON) is a prevalent mycotoxin that is primarily produced by Fusarium spp. and commonly found in various cereal products. Feeding swine diets contaminated with trichothecene DON can lead to major adverse effects, including reduced feed intake, diminished weight gains, and compromised immune function. Among all animal species tested, swine were the most sensitive to DON. Here we explored the disruption of gut health by DON, considering aspects such as intestinal histomorphology, epithelial barrier functions, the intestinal immune system, microflora, and short-chain fatty acid production in the intestines. Numerous additives have been documented for their potential in the detoxification of DON. These additives can alleviate the toxic effects of DON on pigs by modulating the Nrf2-Keap1, mitogen-activated protein kinases (MAPKs) and Nuclear factor kappa-B (NF-κB) signaling pathways. Additionally, there are additives capable of mitigating the toxicity of DON through adsorption or biotransformation. This update has novel potential for advancing our comprehension of the mechanisms linked to DON intestinal toxicity and facilitating the formulation of innovative strategies to mitigate the impact of DON.

Necroptosis contributes to the intestinal toxicity of deoxynivalenol and is mediated by methyltransferase SETDB1

Deoxynivalenol (DON) is a secondary metabolite produced by fungi, which causes serious health issues worldwide due to its widespread presence in human and animal diets. Necroptosis is a newly proposed cell death mode and has been proposed as a potential mechanism of intestinal disease. This study aimed to investigate the role of necroptosis in intestinal damage caused by DON exposure. Piglets were fed diets with or without 4 mg/kg DON for 3 weeks or given a gavage of 2 mg/kg BW DON or sterile saline to investigate the effects of chronic or acute DON exposure on the gut, respectively. IPEC-1 cells were challenged with different concentrations of DON to investigate the effect of DON exposure on the intestinal epithelial cells (IECs) in vitro. Subsequently, the inhibitors of necroptosis were used to treat cells or piglets prior to DON challenge. Chronic and acute DON exposure both caused morphological damage, reduction of disaccharidase activity, decrease of tight junction protein expression, inflammation of the small intestine, and necroptosis of intestinal epithelial cells in piglets. Necroptosis was also detected when IPEC-1 cell damage was induced by DON in vitro. The suppression of necroptosis in IPEC-1 cells by inhibitors (necrostatin-1 (Nec-1), GSK’872, or GW806742X) alleviated cell death, the decrease of tight junction protein expression, oxidative stress, and the inflammatory response induced by DON. Furthermore, pre-treatment with Nec-1 in piglets was also observed to protect the intestine against DON-induced enterotoxicity. Additionally, the expression of histone methyltransferase SETDB1 was abnormally downregulated upon chronic and acute DON exposure in piglets, and necroptosis was activated in IPEC-1 cells due to knockout of SETDB1. Collectively, these results demonstrate that necroptosis of IECs is a mechanism of DON-induced enterotoxicity and SETDB1 mediates necroptosis upon DON exposure in IECs, suggesting the potential for targeted inhibition of necroptosis to alleviate mycotoxin-induced enterotoxicity and intestinal disease.

Identification and characterization of Achromobacter spanius P-9 and elucidation of its deoxynivalenol-degrading potential.

Deoxynivalenol (DON) poses significant challenges due to its frequent contamination of grains and associated products. Microbial strategies for mitigating DON toxicity showed application potential. Eight bacterial isolates with DON degradation activity over 5% were obtained from various samples of organic fertilizer in this study. One of the isolates emerged as a standout, demonstrating a substantial degradation capability, achieving a 99.21% reduction in DON levels. This isolate, underwent thorough morphological, biochemical, and molecular characterization to confirm its identity, and was identified as a new strain of Achromobacter spanius P-9. Subsequent evaluations revealed that the strain P-9 retains its degradation activity after a 24-h incubation, reaching optimal performance at 35°C with a pH of 8.0. Further studies indicated that Ca2+ ions enhance the degradation process, whereas Zn2+ ions exert an inhibitory effect. This is the pioneering report of DON degradation by Achromobacter spanius, illuminating its prospective utility in addressing DON contamination challenges.

Fusariotoxin-Induced Toxicity in Mesenchymal Stem Cells and Fibroblasts: A Comparison Between Differentiated and Undifferentiated Cells.

Humans are unknowingly exposed to mycotoxins through the consumption of plant-derived foods and processed products contaminated with these toxic compounds. In addition to agricultural losses, Fusarium toxins pose a threat to human health. However, the effects of fusariotoxins on the viability and proliferation of stem cells have not been fully explored. We investigated the cytotoxic effects of deoxynivalenol (DON) and B-trichothecene mix (MIX) on mesenchymal stem cells (MSCs) and the L929 fibroblast cell line. MSCs were isolated from the dental pulp tissue. The doubling time and viability of dental pulp stem cells (DPSCs) and L929 cells were determined using the MTT assay. The following doses of B-trichothecenes (0.25-16 µg/mL; 24 hours and 48 hours) were used to evaluate cytotoxicity. In addition, changes in the confluency-dependent response of DPSCs to DON toxicity were determined. Moreover, we investigated the effect of DON on cell death via acridine orange/ethidium bromide (AO/EB) double staining. A DON and MIX showed a dose- and time-dependent inhibitory effect on the proliferation of both cells. DPSCs exposed to DON for 48 hours (IC50 = 0.5 μg/mL) were found to be 16-fold more sensitive than L929 cells (IC50 = 8 μg/mL). Compared with a culture with 80% confluency, DPSCs from a 50% confluent culture were more sensitive to varying doses of DON (0.25-4 µg/mL, 24-48 hours). Moreover, AO/EB staining showed that treatment of DPSCs with DON led to a significant increase in cell death (17% for 2.4 µg/mL; 50% for 4.8 µg/mL). This study reveals that undifferentiated MSCs are significantly more sensitive to DON than differentiated somatic cells (L929). Given that humans are frequently exposed to these mycotoxins, our findings imply that prolonged exposure to them may also have harmful effects on cellular differentiation and embryonic development.

Maintaining the Mitochondrial Quality Control System Was a Key Event of Tanshinone IIA against Deoxynivalenol-Induced Intestinal Toxicity.

Deoxynivalenol (DON) is the one of the most common mycotoxins, widely detected in various original foods and processed foods. Tanshinone IIA (Tan IIA) is a fat-soluble diterpene quinone extracted from Salvia miltiorrhiza Bunge, which has multi-biological functions and pharmacological effects. However, whether Tan IIA has a protective effect against DON-induced intestinal toxicity is unknown. In this study, the results showed Tan IIA treatment could attenuate DON-induced IPEC-J2 cell death. DON increased oxidation product accumulation, decreased antioxidant ability and disrupted barrier function, while Tan IIA reversed DON-induced barrier function impairment and oxidative stress. Furthermore, Tan IIA dramatically improved mitochondrial function via mitochondrial quality control. Tan IIA could upregulate mitochondrial biogenesis and mitochondrial fusion as well as downregulate mitochondrial fission and mitochondrial unfolded protein response. In addition, Tan IIA significantly attenuated mitophagy caused by DON. Collectively, Tan IIA presented a potential protective effect against DON toxicity and the underlying mechanisms were involved in mitochondrial quality control-mediated mitophagy.

DON induced DNA damage triggers absence of p53-mediated G2 arrest and apoptosis in IPEC-1 cells

Deoxynivalenol (DON) stands among the prevalent mycotoxins, and usually contaminates cereal foods and animal feed, leading to human and animal clinical poisoning symptoms such as abdominal pain, diarrhea, and vomiting. To date, the mechanism of toxicity of DON in different mammalian cells is not fully elucidated. In this study, we explored the detrimental impacts of DON on porcine intestinal epithelial cells (IPEC-1), serving as a representative model for porcine intestinal epithelial cells. After treating cells with DON for 24 h, DON can significantly inhibit the activity of cells, induce the production of reactive oxygen species (ROS), significantly reduce the content of glutathione and the activity of catalase, and increase the activity of superoxide dismutase and malondialdehyde, leading to an imbalance in intracellular redox status. In addition, DON can induce DNA double-strand breaks, and decrease mitochondrial membrane potential. Furthermore, DON can promote the release of Cyt C through changes in mitochondrial permeability through inhibit the expression of B-cell lymphoma 2 (Bcl-2) proteins, leading to apoptosis through the mitochondrial pathway. On the other hand, we found that DON can cause IPEC-1 cells G2 phase cycle arrest. Different with our pervious study, DON induces cell cycle arrest in the G2 phase only by activating the ATM-Chk2-Cdc 25 C pathway, but cannot regulate the cell cycle arrest via the ATM-p53 pathway. These results indicate that DON can induce the same toxic phenotype in different cells, but its toxic mechanism is different. All these provide a rationale for revealing DON induced cytotoxicity and intestinal diseases.

Lycopene Maintains Mitochondrial Homeostasis to Counteract the Enterotoxicity of Deoxynivalenol.

The intestinal tract is a target organ for Deoxynivalenol (DON) absorption and toxicity. Mitochondrial homeostasis imbalance is the gut toxicity mechanism of DON. Lycopene (LYC) has intestinal protective effects and can maintain mitochondrial homeostasis in response to various danger signals. The purpose of this study was to explore the protective effect of LYC on DON-induced IPEC-J2 cells damage. These results showed that DON exposure induced an increase in the levels of malondialdehyde and reactive oxygen species (ROS) in IPEC-J2 cells. DON impaired IPEC-J2 cell barrier function and caused mitochondrial dysfunction by inducing mitochondrial permeability transition pore (MPTP) opening, mitochondrial membrane potential (MMP) reducing, destroying mitochondrial fission factors, mitochondrial fusion factors, and mitophagy factors expression. However, adding LYC can reduce the toxic effects of DON-induced IPEC-J2 cells and decrease cellular oxidative stress, functional damage, mitochondrial dynamics imbalance, and mitophagy processes. In conclusion, LYC maintains mitochondrial homeostasis to counteract the IPEC-J2 cells' toxicity of DON.

Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be accomplished effectively using protective agents. This review provides an overview of multiple studies on a wide range of protective agents and their molecular mechanisms against DON organ toxicity. Protective agents include plant extracts, yeast products, bacteria, peptides, enzymes, H2, oligosaccharides, amino acids, adsorbents, vitamins and selenium. Among these, biological detoxification of DON using microorganisms to reduce the toxicity of DON without affecting the growth performance of pigs may be the most promising detoxification strategy. This paper also evaluates future developments related to DON detoxification and discusses the detoxification role and application potential of protective agents. This paper provides new perspectives for future research and development of safe and effective feed additives.

Deoxynivalenol: Emerging Toxic Mechanisms and Control Strategies, Current and Future Perspectives.

Deoxynivalenol (DON) is the most frequently present mycotoxin contaminant in food and feed, causing a variety of toxic effects in humans and animals. Currently, a series of mechanisms involved in DON toxicity have been identified. In addition to the activation of oxidative stress and the MAPK signaling pathway, DON can activate hypoxia-inducible factor-1α, which further regulates reactive oxygen species production and cancer cell apoptosis. Noncoding RNA and signaling pathways including Wnt/β-catenin, FOXO, and TLR4/NF-κB also participate in DON toxicity. The intestinal microbiota and the brain-gut axis play a crucial role in DON-induced growth inhibition. In view of the synergistic toxic effect of DON and other mycotoxins, strategies to detect DON and control it biologically and the development of enzymes for the biodegradation of various mycotoxins and their introduction in the market are the current and future research hotspots.