Individual and combined cytotoxic effects of Fusarium toxins (deoxynivalenol, nivalenol, zearalenone and fumonisins B1) on swine jejunal epithelial cells

Fusarium mycotoxins occur worldwide in foods such as cereals and animal forages, leading to acute and chronic exposures in human and animals. Intestinal epithelial cells (IECs) are an important first target site for these dietary toxins. This study investigated the cytotoxicity of four common Fusarium mycotoxins, deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA) and fumonisin B1 (FB1) on a normal porcine jejunal epithelial cell line, IPEC-J2. A dose response relationship between individual mycotoxins and cell viability (MTT assay) was initially investigated, and subsequently cytotoxic and non-cytotoxic concentrations were selected to investigate combinations of two, three and all four of the mycotoxins. For individual mycotoxins, a dose response was observed with cell viability, such that the potency ranking was NIV > DON > ZEA > FB1. At cytotoxic doses of individual mycotoxins, all mixtures gave reduced cell viability compared to control. At noncytotoxic concentrations of individual mycotoxins, all mixtures were cytotoxic with DON-NIV, DON-ZEA, DON-NIV-FB1, DON-ZEA-FB1, NIV-ZEA-FB1 and all four mixed causing the greatest loss of cell viability. The latter observation in particular raises concerns over safety margins based on single toxin species, and suggests that the effects of multiple complex mixtures need to be better understood to assess health risks.