Toxic mechanisms of the trichothecenes T-2 toxin and deoxynivalenol on protein synthesis.

The toxic mechanisms of trichothecenes, including T-2 toxin and deoxynivalenol (DON), are closely related with their effects on protein synthesis. Increasing lines of evidence show that T-2 toxin can reduce the levels of tight junction proteins, and nuclear factor erythroid 2-related factor 2 (Nrf2) by disrupting cellular barriers and the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Nrf2/heme oxygenase (HO)-1 pathways. Moreover, it can inhibit aggrecan synthesis, thus causing Kashin-Beck disease. Regarding type B trichothecene, DON inhibits activation marker and β-catenin synthesis by acting on immune cells and the wingless/integrated (Wnt) pathway; it also inhibits cell proliferation and immune surveillance. In addition, DON has been shown to destroy tight junctions, glucose transport, and tumor endothelial marker 8, thus disturbing intestinal function and changing cell migration. This review summarizes the inhibitory effects of the trichothecenes T-2 toxin and DON on different protein synthesis, while discussing their underlying mechanisms. Focus is given to the effects of these toxins on tight junctions, aggrecan, activation markers, and hormones including testosterone under the influence of steroidogenic enzymes. This review can extend the current understanding of the effects of trichothecenes on protein synthesis and help to further understand their toxic mechanisms.