Cytotoxicity induced by ochratoxin A, zearalenone, and α-zearalenol: Effects of individual and combined treatment

This study investigated the cytotoxicity of combined mycotoxins of ochratoxin A (OTA), zearalenone (ZEA), and/or α-zearalenol (α-ZOL). The cytotoxicity of two mycotoxin combinations (two two-toxin combinations and one three-toxin combination) on human Hep G2 cells was evaluated using a tetrazolium salt (MTT) assay and isobologram analysis. Our results demonstrated significant cytotoxic effects of the two-toxin combination and the three-toxin combination on Hep G2 cells in a time- and concentration-dependent manner. The combination indexes (CI) were 2.73–7.67 for the OTA + ZEA combination and 1.23–17.82 for the OTA + α-ZOL combination after 24 h, 48 h, and 72 h of exposure at all inhibit concentration (IC) levels (IC10–IC90), indicating an antagonism. The CIs of the ZEA + α-ZOL combination were 1.29–2.55 after 24 h and 72 h of exposure (IC10–IC90), indicating an antagonism. The CIs of the ZEA + α-ZOL combination were 0.74–1.68 after 48 h of exposure, indicating synergism (IC80–IC90), additive effects (IC50–IC70), or antagonism (IC10–IC40). For the OTA + ZEA + α-ZOL combination, the CIs were 1.41–14.65 after 24 h, 48 h, and 72 h of exposure (IC10–IC90), indicating an antagonism.