Selenium Improves Bone Microenvironment-Related Hematopoiesis and Immunity in T-2 Toxin-Exposed Mice

Zhang, Jian; Han, Yaling; Song, Miao; Wang, Qi; Cao, Zheng; Yang, Xu; Li, Yanfei

doi:10.1021/acs.jafc.2c08275

Cited by 7 publications

(2 citation statements)

References 60 publications

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“…40 Moreover, T-2 toxin is stable in nature and difficult to completely remove from food and feed, which poses a serious threat to human and animal health. 41 Also, T-2 toxin can cause liver DNA breakage, 42 induce liver oxidative stress and apoptosis, 9,12,43 and induce the expression of liver inflammatory factors, leading to liver injury, 32 which seriously endangers the health of animals and humans. However, there is no effective antagonist to alleviate liver injury caused by T-2 toxin due to the lack of key targets and corresponding drugs for the liver injury.…”

Section: ■ Discussionmentioning

confidence: 99%

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Xu,

Wu,

Zhao

et al. 2024

J. Agric. Food Chem.

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Multiple compounds are related to the development of liver injury, such as toxins, drugs, and environmental pollutants. Although there are reports that the T-2 toxin can cause liver injury, its toxic mechanism remains unclear, which further impedes the development of effective antidotes. In this study, CRISPR-Cas9 genome-wide screening technology was used to identify transformation-related protein 53 inducible nuclear protein 1 (trp53inp1) as a toxic target of the T-2 toxin. Mechanism studies have shown that the T-2 toxin induced pyroptosis of macrophages (J774A.1 cells) by activating the trp53inp1/NF-κB/NLRP3/GSDMD-N pathway, leading to a subacute liver injury. Also, the new drug berberine (BER) identified through virtual screening significantly alleviated the subacute liver injury by competitively binding trp53inp1 via His224; the effect was better than those of the positive control drugs N-acetylcysteine (NAC) and disulfiram (DSF). In summary, the above results indicate that trp53inp1 is a key target for T-2 toxin to induce subacute liver injury and that inhibiting macrophage pyroptosis is a new method for treating liver injury. In addition, this study provides a new method and strategy for the discovery of key disease targets and the search for effective drugs.

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Section: ■ Discussionmentioning

confidence: 99%

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Xu,

Wu,

Zhao

et al. 2024

J. Agric. Food Chem.

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“…Combined with the KEGG enrichment analysis results of the T-2 group vs. the control group, it was shown that the T-2 toxin could induce apoptosis, whereas SeMet indirectly antagonized apoptosis. Oxidative stress and apoptosis have been shown to occur in mice exposed to the T-2 toxin, and apoptosis was alleviated after treatment with Se [ 46 ]. Moreover, the apoptosis pathway was significantly enriched in the T-2 + SeMet group vs. the T-2 group, and the autophagy pathway appeared simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Selenomethionine Antagonized microRNAs Involved in Apoptosis of Rat Articular Cartilage Induced by T-2 Toxin

Luo

Wang

et al. 2023

Toxins

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T-2 toxin and selenium deficiency are considered important etiologies of Kashin–Beck disease (KBD), although the exact mechanism is still unclear. To identify differentially expressed microRNAs (DE-miRNAs) in the articular cartilage of rats exposed to T-2 toxin and selenomethionine (SeMet) supplementation, thirty-six 4-week-old Sprague Dawley rats were divided into a control group (gavaged with 4% anhydrous ethanol), a T-2 group (gavaged with 100 ng/g·bw/day T-2 toxin), and a T-2 + SeMet group (gavaged with 100 ng/g·bw/day T-2 toxin and 0.5 mg/kg·bw/day SeMet), respectively. Toluidine blue staining was performed to detect the pathological changes of articular cartilage. Three rats per group were randomly selected for high-throughput sequencing of articular cartilage. Target genes of DE-miRNAs were predicted using miRanda and RNAhybrid databases, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were enriched. The network map of miRNA-target genes was constructed using Cytoscape software. The expression profiles of miRNAs associated with KBD were obtained from the Gene Expression Omnibus database. Additionally, the DE-miRNAs were selected for real-time quantitative PCR (RT-qPCR) verification. Toluidine blue staining demonstrated that T-2 toxin damaged articular cartilage and SeMet effectively alleviated articular cartilage lesions. A total of 50 DE-miRNAs (28 upregulated and 22 downregulated) in the T-2 group vs. the control group, 18 DE-miRNAs (6 upregulated and 12 downregulated) in the T-2 + SeMet group vs. the control group, and 25 DE-miRNAs (5 upregulated and 20 downregulated) in the T-2 + SeMet group vs. the T-2 group were identified. Enrichment analysis showed the target genes of DE-miRNAs were associated with apoptosis, and in the MAPK and TGF-β signaling pathways in the T-2 group vs. the control group. However, the pathway of apoptosis was not significant in the T-2 + SeMet group vs. the control group. These results indicated that T-2 toxin induced apoptosis, whereas SeMet supplementation antagonized apoptosis. Apoptosis and autophagy occurred simultaneously in the T-2 + SeMet group vs. T-2 group, and autophagy may inhibit apoptosis to protect cartilage. Compared with the GSE186593 dataset, the evidence of miR-133a-3p involved in apoptosis was more abundant. The results of RT-qPCR validation were consistent with RNA sequencing results. Our findings suggested that apoptosis was involved in articular cartilage lesions induced by T-2 toxin, whereas SeMet supplementation antagonized apoptosis, and that miR-133a-3p most probably played a central role in the apoptosis process.

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Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

Yang,

Tang,

et al. 2024

Nano Res.

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Selenium Improves Bone Microenvironment-Related Hematopoiesis and Immunity in T-2 Toxin-Exposed Mice

Cited by 7 publications

References 60 publications

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Selenomethionine Antagonized microRNAs Involved in Apoptosis of Rat Articular Cartilage Induced by T-2 Toxin

Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

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