Zearalenone (ZEA) is the most common fungal toxin contaminating livestock and poultry feeding, especially in pigs, causing severe toxic effects and economic losses. However, the mechanism of ZEA damage to the intestine is unknown. We constructed an in vitro model of ZEA toxicity in a porcine small intestinal epithelial cell (IPEC-J2) line. ZEA causes severe oxidative stress in porcine small intestine cells, such as the production of ROS and a significant decrease in the levels of antioxidant enzymes GSH, CAT, SOD, and T-AOC. ZEA also caused apoptosis in porcine small intestine cells, resulting in a significant reduction in protein and/or mRNA expression of apoptosis-related pathway factors such as P53, caspase 3, caspase 9, Bax, and Cyt-c, which in turn caused a significant decrease in protein and/or mRNA expression of inflammatory-related factors such as IL-1β, IL-2, Cox-2, NF-κD, NLRP3, IL-6, and IL -18, which in turn caused a significant increase in protein and/or mRNA expression levels. The final results suggest that ZEA can cause a severe toxic response in porcine small intestine cells, with oxidative stress, apoptotic cell death and inflammatory damage.

The role of gut microbiota has become a research hotspot in recent years; however, whether the gut microbiota are involved in the alleviation or exacerbation of Deoxynivalenol (DON) toxicity has not been fully studied. Therefore, the objective of this study was to investigate whether the gut microbiota are involved in reducing or aggravating the intestinal damage induced by DON in mice. Mice that received or did not receive antibiotic-induced intestinal flora clearance were orally given DON (5 mg kg/bw/day) for 14 days. At the end of the experiment, serum, intestinal tissue samples and colon contents were collected for further analysis. DON caused development of severe histopathological damage, such as necrosis and inflammation of the jejunum and colon in mice without gut microbiota clearance. The levels of tight junction proteins ZO-1 and occludin were reduced in the jejunum and colon of mice without gut microbiota clearance. In addition, the mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased in mice without gut microbiota clearance. The presence of microbiota exacerbate the intestinal damage induced by DON via changes in gut microbiota abundance and production of gut damaging metabolites.

Background/Objectives: Deoxynivalenol (DON), known as vomitoxin, is one of the most common mycotoxins produced by Fusarium graminearum, with high detection rates in feed worldwide. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation and the accumulation of reactive oxygen species. Although it has been demonstrated that DON can induce ferroptosis in the liver, the specific mechanisms and pathways are still unknown. The aim of this experiment was to investigate that DON can induce iron metabolism disorders in the livers of mice, thereby triggering ferroptosis and causing toxic damage to the liver. Methods: Male C57 mice were treated with DON at a 5 mg/kg BW concentration as an in vivo model. After sampling, organ coefficient monitoring, liver function test, histopathological analysis, liver Fe²⁺ content test, and oxidative stress-related indexes were performed. The mRNA and protein expression of Nrf2 and its downstream genes were also detected using a series of methods including quantitative real-time PCR, immunofluorescence double-labeling, and Western blotting analysis. Results: DON can cause damage to the liver of a mouse. Specifically, we found that mouse livers in the DON group exhibited pathological damage in cell necrosis, inflammatory infiltration, cytoplasmic vacuolization, elevated relative liver weight, and significant changes in liver function indexes. Meanwhile, the substantial reduction in the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the DON group indicated that DON also caused oxidative stress in the liver. Notably, DON exposure increased the levels of Fe²⁺ and Malondialdehyde (MDA) in the liver, which provides strong evidence for the occurrence of iron metabolism and ferroptosis disorders. Most importantly, mRNA and protein expression of Nrf2, an important pathway for iron metabolism and ferroptosis, along with its downstream genes, heme oxygenase (HO-1), quinone oxidoreductase (NQO1), glutathione peroxidase (GPX4), and solute carrier gene (SLC7a11), were significantly inhibited in the DON group. Conclusions: Based on our results, the Nrf2 pathway is closely associated with DON-induced iron metabolism disorders and ferroptosis in mouse livers, suggesting that maintaining hepatic iron homeostasis and activating the Nrf2 pathway may be a potential target for mitigating DON hepatotoxicity in the future.

Background: Deoxynivalenol (DON) poses a threat to animal and human health, particularly causing damage to the nervous system. Intestinal flora can regulate the nervous system through the gut–brain axis; however, there is currently a lack of evidence on the effect of changing the intestinal flora on the damage to the nervous system caused by DON. Therefore, this study aims to investigate the effect of gut microbiota ablation on neurotoxicity induced by exposure to deoxynivalenol. Methods: One hundred-twenty (120) specific pathogen-free (SPF) male C57BL/6j mice were randomly divided into four groups (control group, microbiota-uncleaned group + 5 mg/kg/BW DON, microbiota-cleared group, and microbiota-cleared group + 5 mg/kg/BW DON). The open field and Morris behavior tests were used to evaluate behavior changes after DON exposure. After 14 days of treatment, the mice were euthanized and brain tissues were collected for further analysis. Results: The tests showed that DON exposure led to anxiety and decreased learning ability in mice with no gut microbiota ablation. We also observed pathological changes including neuronal shrinkage, degeneration, and cortical edema in the mice with no microbiota ablation after DON exposure. In addition, the protein and mRNA levels of tight junction proteins and anti-inflammatory factors were decreased in the mice with no microbiota ablation after DON exposure compared with mice with ablated microbiota. Conclusions: We concluded that the presence of microbiota plays a key role in the neurotoxicity induced by DON; thus, ablation of the intestinal microbiota can effectively improve brain damage caused by DON.