Toxicity and metabolic effect of combined deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol on a Caco-2 cell model

Abstract

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-acetylDON), and 15-acetyldeoxynivalenol (15-acetylDON) are typical type-B trichothecenes produced by Fusarium commonly found in cereals worldwide. Details on the combined toxicity of these mycotoxins remain insufficient. In this study, human colorectal adenocarcinoma Caco-2 cell line was used to analyze the individual and combined toxic effects, together with the potential cytotoxic mechanism, of DON, 3-acetylDON, and 15-acetylDON. DON exerted the highest inhibitory rate of cell viability, followed by 15-acetylDON and 3-acetylDON. The binary and ternary combinations exerted an antagonistic effect on Caco-2 cells at IC50–IC90 treatment doses; meanwhile, 3-acetylDON + 15-acetylDON at low doses exhibited additive effects, and DON + 15-acetylDON and DON + 3-acetylDON + 15-acetylDON showed synergistic effects. The apoptotic rate and reactive oxygen species level of DON + 3-acetylDON were lower than those of DON alone. When Caco-2 cells were treated with trichothecenes individually or in combination, Bcl-2 was significantly down-regulated, and Bax, p53, and caspases genes were up-regulated. Moreover, DON and its acetylated derivatives disrupted amino acid metabolism and protein synthesis. These results indicate that the toxicological effects of trichothecene combinations varied depending on the type of combination and concentration. The co-exposure of DON and its derivatives may induce apoptosis of Caco-2 cells by inhibiting protein synthesis, inducing oxidative stress, and regulating the level of apoptosis-related genes. These findings can provide new vision for proposing intervention strategies for co-exposure toxicity of DON and its acetylated derivatives.