Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells

This study was performed to determine the individual and combined cytotoxic effects of Aflatoxin B-1 (AFB(1),), zearalenone (ZEA), deoxynivalenol (DON) and fumonisin B-1 (FB1) on BRL 3A rat liver cells. After the mycotoxins treated the BRL 3A cells for 12, 24 and 48 h, cell viability was determined using the mu assay. The cytotoxicity of individual mycotoxins on BRL 3A cell viability in decreasing order were DON > AFB(1) > ZEA > FB1. The central composite design (CCD) was used to assess the toxicity of binary and ternary mixtures of these mycotoxins. The mixtures of AFB(1) + ZEA and AFB(1) + DON showed the synergetic toxic effects on BRL 3A cells. These toxins decreased the viability of cells by inducing intracellular reactive oxygen species (ROS) production and promoting apoptosis in the BRL 3A cells. This effect was mediated by an upregulation of the stress and apoptotic genes Hsp70, p53, Bax, Caspase-3 and Caspase-8, along with a downregulation of the antiapoptotic gene Bcl-2. In conclusion, our results suggested that the coexistence of AFB(1) and ZEA or DON in agricultural products could be more hepatotoxic than individually, suggests that the toxicological interactions of these toxins need to be better understood to assess health risks. (C) 2015 Elsevier Ltd. All rights reserved.