Deoxynivalenol (DON) is a mycotoxin that is found in feed ingredients derived from grains such as corn and wheat. Consumption of DON-contaminated feed has been shown to cause damage to the intestine, kidneys, and liver. However, the molecular mechanism by which DON exerts its effect in the small intestine is not completely understood. As a result, we profiled gene expression in intestinal epithelial cells treated with DON and examined the molecular function in vitro. We hypothesized that DON could induce apoptosis via the FOXO3a-signaling pathway in intestinal epithelial cells based on these findings. DON induced the apoptosis and the translocation of FOXO3a into the nucleus. Moreover, the inhibiting of FOXO3a alleviated the apoptosis and expression of apoptosis-related genes (TRAL, BCL-6, CASP8, and CASP3). ERK1/2 inhibitor treatment suppressed the translocation of FOXO3a into the nucleus. Our discovery suggests that DON induces apoptosis in intestinal epithelial cells through the FOXO3a-signaling pathway.

Deoxynivalenol (DON) is known as a vomitoxin, which frequently contaminates feedstuffs, such as corn, wheat, and barley. Intake of DON-contaminated feed has been known to cause undesirable effects, including diarrhea, emesis, reduced feed intake, nutrient malabsorption, weight loss, and delay in growth, in livestock. However, the molecular mechanism of DON-induced damage of the intestinal epithelium requires further investigation. Treatment with DON triggered ROS in IPEC-J2 cells and increased the mRNA and protein expression levels of thioredoxin interacting protein (TXNIP). To investigate the activation of the inflammasome, we confirmed the mRNA and protein expression levels of the NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP-1). Moreover, we confirmed that caspase mediates the mature form of interleukin-18, and the cleaved form of Gasdermin D (GSDMD) was increased. Based on these results, our study suggests that DON can induce damage through oxidative stress and pyroptosis in the epithelial cells of the porcine small intestine via NLRP3 inflammasome.

Deoxynivalenol (DON) is a mycotoxin derived from Fusarium species. It is commonly found in crops and has a high detection rate in animal feedstuffs. We previously confirmed that apoptosis could be induced by DON through the FOXO3a (Forkhead box 3a) signaling pathway. In this study, to identify a natural compound to mitigate DON-induced apoptosis via FOXO3a, we performed high-throughput screening. We found that ivangustin (IVAN) alleviated DON-induced cytotoxicity. It also decreased DON-mediated apoptosis and the expression levels of apoptosis-associated genes at the mRNA level. Furthermore, treatment with IVAN inhibited FOXO3a from translocating into the nucleus. The results demonstrated the mitigating effects of the natural compound IVAN on DON-induced apoptosis through the FOXO3a signaling pathway. This study focused on elucidating the mechanism underlying damage caused by DON. According to the results of this study, novel alternatives to mitigate DON cytotoxicity may be developed. This study could provide fundamental data for the formulation of mycotoxin alleviation strategies to improve pig productivity.

Fumonisin B1 (FB1) is a mycotoxin commonly found in animal feed, particularly in corn-based products. Exposure to FB1 can damage multiple organs, including the intestine, but its molecular effects on intestinal epithelial cells remain incompletely understood. This study investigated FB1-induced toxicity in porcine intestinal epithelial (IPEC-J2) cells and screened natural products for protective effects. Exploratory gene expression profiling identified genes showing predefined expression changes following FB1 exposure, and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated associations with apoptosis-related processes. Annexin V/propidium iodide staining showed increased apoptosis-associated staining, while quantitative real-time polymerase chain reaction (qRT-PCR) showed altered expression of BCL2, CASP3, and CASP9. To identify protective candidates, 332 natural products were evaluated using high-throughput screening. Among the screened extracts, C. communis showed the highest cell viability in the primary screening and was selected for further investigation. Co-treatment with C. communis was associated with reduced apoptosis-associated staining and partial counteraction of FB1-associated changes in apoptosis-related gene expression. These findings suggest that C. communis warrants further investigation as a natural product for mitigating FB1-associated intestinal epithelial toxicity.