Individual and combined cytotoxicity assessment of zearalenone with ochratoxin A or α-zearalenol by full factorial design

The combined mycotoxins zearalenone (ZEA) with ochratoxin A (OTA) or alpha-zearalenol (alpha-ZOL) are frequently found together in milk. Toxicological data concerning the combined effects of these mycotoxins are sparse. In present study, individual and combined ZEA, OTA and alpha-ZOL caused cytotoxicity and oxidative damage, including reductions in intracellular superoxide dismutase and glutathione peroxidase activities and glutathione content, along with increases in malonaldehyde content on human Hep G2 cells after 48 h of exposure. Among individual mycotoxins, OTA had the greatest cytotoxic effect followed by alpha-ZOL. Compared with individual mycotoxins, combinations produced more serious negative effects, more importantly, ZEA + OTA was antagonistic for these effects, whereas ZEA + alpha-ZOL was antagonistic at low concentrations, but synergistic at high concentrations of ZEA, which were evaluated by 3 x 3 full factorial analysis and estimated marginal means plots. Our results also demonstrated a significant correlation between cytotoxicity and oxidative damage in response to these combinations.