An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50017004" target="_blank" >RIV/62690094:18470/20:50017004 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007/s00204-020-02899-9" target="_blank" >https://link.springer.com/article/10.1007/s00204-020-02899-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-020-02899-9" target="_blank" >10.1007/s00204-020-02899-9</a>

Result language

angličtina

Original language name

An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment

Original language description

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 &apos;,4 &apos;-dihydroxy-T-2 toxin and 4 &apos;,4 &apos;-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3 &apos;-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, &quot;immune evasion&quot; 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Archives of toxicology

ISSN

0340-5761

e-ISSN

—

Volume of the periodical

94

Issue of the periodical within the volume

11

Country of publishing house

DE - GERMANY

Number of pages

25

Pages from-to

3645-3669

UT code for WoS article

000568157900003

EID of the result in the Scopus database

2-s2.0-85090794673