Individual and Combined Effect of Zearalenone Derivates and Beauvericin Mycotoxins on SH-SY5Y Cells

Beauvericin (BEA) and zearalenone derivatives, alpha-zearalenol (alpha-ZEL), and beta-zearalenol (beta-ZEL), are produced by several Fusarium species. Considering the impact of various mycotoxins on human's health, this study determined and evaluated the cytotoxic effect of individual, binary, and tertiary mycotoxin treatments consisting of alpha-ZEL, beta-ZEL, and BEA at different concentrations over 24, 48, and 72 h on SH-SY5Y neuronal cells, by using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide). Subsequently, the isobologram method was applied to elucidate if the mixtures produced synergism, antagonism, or additive effects. Ultimately, we determined the amount of mycotoxin recovered from the media after treatment using liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-qTOF-MS). The IC50 values detected at all assayed times ranged from 95 to 0.2 mu M for the individual treatments. The result indicated that beta-ZEL was the most cytotoxic mycotoxin when tested individually. The major effect detected for all combinations assayed was synergism. Among the combinations assayed, alpha-ZEL + beta-ZEL + BEA and alpha-ZEL + BEA presented the highest cytotoxic potential with respect to the IC value. In individual treatment, alpha-ZEL was the most recovered mycotoxin; while, this was observed for BEA in binary combination alpha-ZEL + BEA.