An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment
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REVIEW ARTICLE
An update on T‑2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment Qinghua Wu1,3 · Zihui Qin2 · Kamil Kuca3 · Li You1 · Yingying Zhao1 · Aimei Liu4 · Kamil Musilek3 · Zofia Chrienova3 · Eugenie Nepovimova3 · Patrik Oleksak3 · Wenda Wu2,3 · Xu Wang4 Received: 24 August 2020 / Accepted: 1 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3′,4′-dihydroxy-T-2 toxin and 4′,4′-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3′-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2–3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2–3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, “immune evasion” activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2–4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms. Keywords T-2 toxin · Modified T-2 toxin · Metabolism · Immunotoxicity · Human exposure assessments · Biomarkers
Qinghua Wu and Zihui Qin contributed equally to this work. * Wenda Wu [email protected] * Xu Wang [email protected] 1
College of Life Science, Yangtze University, Jingzhou 434025, China
2
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
3
Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
4
National Reference Laboratory of Veterinary Dru
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