Metabolomic profiling reveals similar cytotoxic effects and protective functions of quercetin during deoxynivalenol- and 15-acetyl deoxynivalenol-induced cell apoptosis

Among the family of mycotoxins of deoxynivalenol (DON) detected in nature, high proportions of 15-acetyldeoxynivalenol (15ADON) co-occur with the prototype DON and increase the combined exposure and synergistic health risks. The current study aimed to explore the mechanisms underlying the toxicity of 15ADON and compare them with those of DON. As the natural flavonoid compound quercetin (QUE) possesses antioxidant properties, we also aimed to determine the antioxidant effects of QUE on the tested mycotoxins. First, the global metabolomics approach was applied and showed that the metabolites produced from 15ADON or DON were almost identical, while QUE reversed the changes in the levels of key metabolites. Specifically, both DON and 15ADON activated the cell apoptosis pathway mediated by p38 and JNK, but inhibited the cell survival pathway mediated by ERK1/2 in GES-1 cells. Simultaneously, 15ADON induced FOXO3a nuclear translocation, similar to the results described for DON in our recent report. Furthermore, the addition of QUE appeared to counteract the detrimental effects of 15ADON and DON. We observed the effects of QUE treatment on mutant yeast strains with defects in their antioxidant system. More interestingly, QUE also substantially restored the increased ROS levels and the inhibited the growth rate following exposure to the mycotoxins DON and 15ADON. The data reported here support the hypothesis that QUE rescues the toxic effects of DON or 15ADON due to the similar mechanisms of DON and 15ADON toxicity.