Abstract
Mycotoxins are highly diverse secondary metabolites produced in nature by a wide variety of fungi. Mycotoxins cause animal feed and food contamination, resulting in mycotoxicosis. T-2 toxin is one of the most common and toxic trichothecene mycotoxins. For the last decade, it has garnered considerable attention due to its potent neurotoxicity. Worryingly, T-2 toxin can cross the blood–brain barrier and accumulate in the central nervous system (CNS) to cause neurotoxicity. This review covers the current knowledge base on the molecular mechanisms of T-2 toxin-induced oxidative stress and mitochondrial dysfunction in the CNS. In vitro and animal data have shown that induction of reactive oxygen species (ROS) and oxidative stress plays a critical role during T-2 toxin-induced neurotoxicity. Mitochondrial dysfunction and cascade signaling pathways including p53, MAPK, Akt/mTOR, PKA/CREB and NF-κB contribute to T-2 toxin-induced neuronal cell death. T-2 toxin exposure can also result in perturbations of mitochondrial respiratory chain complex and mitochondrial biogenesis. T-2 toxin exposure decreases the mitochondria unfolded protein response and dampens mitochondrial energy metabolism. Antioxidants such as N-acetylcysteine (NAC), activation of Nrf2/HO-1 and autophagy have been shown to provide a protective effect against these detrimental effects. Clearly, translational research and the discovery of effective treatment strategies are urgently required against this common food-borne threat to human health and livestock.
Article Highlights
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(1)
This review covers the main signaling pathways and molecular mechanisms of T-2 toxin induced neurotoxicity.
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(2)
Oxidative stress and mitochondria dysfunction play a critical role during T-2 toxin induced neurotoxicity.
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(3)
Perturbations to the mitochondrial respiratory chain complex and mitochondrial biogenesis occur as a result of T-2 toxin exposure.
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(4)
T-2 toxin exposure results in perturbed mitochondria unfolded protein response and mitochondrial energy metabolism.
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(5)
T-2 toxin can induce the activation of autophagy and mitophagy which play a protective role.
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Acknowledgements
S.T. and X.X. were supported by the Key Projects in Chinese National Science and Technology Pillar Program during the 12th Five-Year Plan Period (No. 2015BAD11B03) and the National Key Research and Development Program of China (Project No. 2018YFC1603005).
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Dai, C., Xiao, X., Sun, F. et al. T-2 toxin neurotoxicity: role of oxidative stress and mitochondrial dysfunction. Arch Toxicol 93, 3041–3056 (2019). https://doi.org/10.1007/s00204-019-02577-5
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DOI: https://doi.org/10.1007/s00204-019-02577-5