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T-2 toxin, a type A trichothecene, is a secondary metabolite produced by Fusarium poae, Fusarium sporotrichioides, and Fusarium tricinctum. As the most toxic trichothecenes, T-2 toxin causes severe damage to multiple organs, especially to liver. However, the contamination of T-2 toxin covers a wide range of plants, including nuts, grains, fruits and herbs globally. And due to chemical stability of T-2 toxin, it is difficult to be completely removed from the food and feeds, which poses a great threat to human and animal health. Liver is the major detoxifying organ which also makes it the main target of T-2 toxin. After being absorbed by intestine, the first pass effect will reduce the level of T-2 toxin in blood indicating that liver is the main metabolic site of T-2 toxin in vivo. In this review, updated researches on the hepatotoxicity of T-2 toxin were summarized. The metabolic characteristic of T-2 toxin in vivo was introduced. The main hepatotoxic mechanisms of T-2 toxin are oxidative stress, mitochondrial damage, deoxyribonucleic acid (DNA) methylation, autophagy and apoptosis. The remission of the hepatotoxicity induced by T-2 toxin was also studied in this review followed by new findings on the detoxification of hepatotoxicity induced by T-2 toxin. The review aimed to offer a comprehensive view and proposes new perspectives in the field of hepatotoxicity induced by T-2 toxin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

T-2 toxin is an unavoidable food and feed contaminant that seriously threatens human and animal health. Exposure to T-2 toxin can cause testosterone synthesis disorder in male animals, but the molecular mechanism is still not completely clear. The MAPK pathway participates in the regulation of testosterone synthesis by Leydig cells, but it is unclear whether the MAPK pathway participates in T-2 toxin-induced testosterone synthesis disorders. In this research, testosterone synthesis capacity, testosterone synthase expression and MAPK pathway activation were examined in male mice and TM3 cells exposed to T-2 toxin. The results showed that T-2 toxin exposure decreased testicular volume and caused pathological changes in the microstructure and ultrastructure of testicular Leydig cells. T-2 toxin exposure also decreased testicular testosterone content and the protein expression of testosterone synthase. In vitro, T-2 toxin inhibited cell viability and decreased the expression of testosterone synthase in TM3 cells, and it decreased the testosterone contents in cell culture supernatants. Moreover, T-2 toxin activated the MAPK pathway by increasing the expression of p38, JNK and ERK as well as the expression of p-p38, p-JNK and p-ERK in testis and TM3 cells. The p38 molecular inhibitor (SB203580) significantly alleviated the T-2 toxin-induced decrease in testosterone synthase expression in TM3 cells and the T-2 toxin-induced reduction in testosterone content in TM3 cell culture supernatants. In summary, p38 mediates T-2 toxin-induced Leydig cell testosterone synthesis disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

T-2 toxin treatment causes male reproduction system dysfunction, although the exact mechanism remains unclear. In this research, male Kunming mice and TM4 cells were treated with varying concentrations of the T-2 toxin for evaluating the adverse effect of T-2 toxin on male reproductive function. MCC950 or NAC was used to block NLRP3 inflammasome activation and eliminate reactive oxygen species (ROS) accumulation in the TM4 cell, respectively. The results showed that: (1) T-2 toxin caused testicular atrophy, destroyed the microstructure and ultrastructure of the testis, and caused sperm deformities; (2) T-2 toxin increased the content and gene expressions of TNF-α and IL-6 and decreased the IL-10 content and gene expression, causing testis and TM4 cell inflammatory injury; (3) T-2 toxin activated NLRP3 inflammasome in the testis and TM4 cells and caused ROS accumulation in the testis; (4) suppressing NLRP3 inflammasome activation using 20 nM MCC950 alleviated the TM4 cell inflammatory damage caused via the T-2 toxin; nevertheless, 20 nM MCC950 did not reduce ROS accumulation in TM4 cells; and (5) NAC relieved the inflammatory damage in TM4 cells by inhibiting NLRP3 inflammasome activation. Taken together, T-2 toxin caused testicular inflammation injury through ROS-mediated NLRP3 inflammasome activation, resulting in male reproductive dysfunction.

T-2 toxin, the most toxic type A trichothecene mycotoxin, is produced by Fusarium, and is widely found in contaminated feed and stored grains. T-2 toxin is physicochemically stable and is challenging to eradicate from contaminated feed and cereal, resulting in food contamination that is inescapable and poses a major hazard to both human and animal health, according to the World Health Organization. Oxidative stress is the upstream cause of all pathogenic variables, and is the primary mechanism through which T-2 toxin causes poisoning. Nuclear factor E2-related factor 2 (Nrf2) also plays a crucial part in oxidative stress, iron metabolism and mitochondrial homeostasis. The major ideas and emerging trends in future study are comprehensively discussed in this review, along with research progress and the molecular mechanism of Nrf2's involvement in the toxicity impact brought on by T-2 toxin. This paper could provide a theoretical foundation for elucidating how Nrf2 reduces oxidative damage caused by T-2 toxin, and a theoretical reference for exploring target drugs to alleviate T-2 toxin toxicity with Nrf2 molecules. [ABSTRACT FROM AUTHOR]