Correction: Xia et al. Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway. Foods 2024, 13, 1217.

In the original publication [...].

Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway.

Zearalenone (ZEA), a mycotoxin widely present in crops and food, poses a major threat to animal and human health. The consumption of ZEA-contaminated food or feed causes intestinal damage. Therefore, exploring how to mitigate the intestinal damage caused by its ZEA is becoming increasingly important. Resveratrol (RSV), a polyphenol compound, mainly exists in Vitis vinifera, Polygonum cuspidatum, Arachis hypogaea, and other plants. It has potent anti-inflammatory and antioxidant activity. The primary objective of this study was to assess the defensive effects of RSV and its molecular mechanism on the intestinal mucosal injury induced by ZEA exposure in mice. The results showed that RSV pretreatment significantly reduced serum DAO and that D-lactate levels altered intestinal morphology and markedly restored TJ protein levels, intestinal goblet cell number, and MUC-2 gene expression after ZEA challenge. In addition, RSV significantly reversed serum pro-inflammatory factor levels and abnormal changes in intestinal MDA, CAT, and T-SOD. Additional research demonstrated that RSV decreased inflammation by blocking the translocation of nuclear factor-kappaB (NF-κB) p65 and decreased oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2) pathway and its associated antioxidant genes, including NQO1, γ-GCS, and GSH-PX. In summary, RSV supplementation attenuates intestinal oxidative stress, inflammation, and intestinal barrier dysfunction induced by ZEA exposure by mediating the NF-κB and Nrf2/HO-1 pathways.

Zearalenone and deoxynivalenol reduced Th1-mediated cellular immune response after Listeria monocytogenes infection by inhibiting CD4+ T cell activation and differentiation.

Based on the fact that mycotoxins and the food-borne bacteria coexist in the natural environment and pose a significant health hazard to humans and animals, it is important to investigate the immunosuppressive mechanism of ZEA (zearalenone), DON (deoxynivalenol), and their combination in bacterial infections. In this study, we established a mouse model of mycotoxin low-dose exposure combined with Listeria monocytogenes infection and investigated the effects of ZEA, DON and their combination on Th1-mediated anti-intracellular bacterial infection based on CD4+ T cell activation and differentiation using both in vitro and in vivo analyses. The present study showed that both ZEA and DON aggravated Listeria monocytogenes infection in mice and affected the activation of CD4+ T cells and Th1 differentiation, including the effects on costimulatory molecules CD28 and CD152 and on cross-linking of IL-12 and IL-12R, by inhibiting T cell receptor (TCR) signaling. When compared with ZEA, DON was found to have a greater impact on many related indicators. Surprisingly, the combined effects of ZEA and DON did not appear to enhance toxicity compared to treatment with the individual mycotoxins. Our findings more clearly revealed that exposure to low-dose ZEA and DON caused immunosuppression in the body by mechanisms including inhibition of CD4+ T cells activation and reduction of Th1 cell differentiation, thus exacerbating infection of animals by Listeria monocytogenes.

Decrease in immune function and the role of mitogen-activated protein kinase (MAPK) overactivation in apoptosis during T lymphocytes activation induced by zearalenone, deoxynivalenol, and their combinations.

Currently there are few reports on the combined immunotoxicity of zearaleone (ZEA) and deoxynivalenol (DON). Since the two coexist naturally, it is necessary to understand the immunotoxicity caused by the two mycotoxins alone and in combination. To examine T lymphocytes activation and immune effect during activation, we used mouse primary spleen T lymphocytes as the experimental material and concanavalin (Con A) as the stimulator. The effects of ZEA, DON, and their combined exposure on T lymphocytes immune related function and the relationship between the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and mycotoxin induced T lymphocytes apoptosis were studied in vitro. Specifically, T lymphocytes were isolated from primary mouse splenic lymphocytes, activated by Con A and then exposed to different concentrations of ZEA, DON, and their combinations. Our results showed that ZEA and DON alone and their combinations (20:1) can decrease the cell viability of T lymphocytes activated by Con A. The inhibitory effect of the combined groups was greater than that of the single mycotoxins, showing a synergistic effect. In addition, single or combined mycotoxins can lead to intracellular and surface ultrastructure damage of T lymphocytes, inhibit the expression of CD25 and CD278 and inhibit the synthesis of effect molecules poreforming protein (PFP), granzyme A (GZMA), and tumor necrosis factor-α (TNF-α). Meanwhile, the single mycotoxin or combined mycotoxins can promote the apoptosis of T lymphocytes which was accompanied by the overactivation of MAPK. After using the inhibitors of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) in the MAPK pathway, we found that the apoptosis of the cells induced by the ZEA was significantly decreased, and the apoptosis of the cells induced by DON had no significant changes. This suggests that the activation of MAPK induced by ZEA can promote the apoptosis of T lymphocytes, but the activation of MAPK induced by DON is not directly related to T cell apoptosis.