Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells
Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells
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DOI：
10.1016/j.toxicon.2014.12.010
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发表时间：
2015-03-01
期刊：
影响因子：
2.8
通讯作者：
Qi, De-Sheng
中科院分区：
文献类型：
--
作者：
Sun, Lv-Hui;Lei, Ming-yan;Qi, De-Sheng
本研究旨在确定黄曲霉毒素B-1（AF B（1））、玉米赤霉烯酮（ZEA）、脱氧雪腐镰刀菌烯醇（DON）和伏马菌素B-1（FB 1）对BRL 3A大鼠肝细胞的单独和联合细胞毒性作用。真菌毒素处理BRL 3A细胞12、24和48 h后，使用μ测定法测定细胞活力。单种真菌毒素对BRL 3A细胞活力的毒性大小依次为DON > AFB（1）> ZEA > FB 1。中心组合设计（CCD）被用来评估这些真菌毒素的二元和三元混合物的毒性。AFB（1）+ ZEA和AFB（1）+ DON对BRL 3A细胞有协同毒性作用。这些毒素通过诱导细胞内活性氧（ROS）的产生和促进BRL 3A细胞的凋亡来降低细胞的活力。这种作用是由应激和凋亡基因HSP 70、p53、Bax、Caspase-3和Caspase-8的上调介导的，沿着抗凋亡基因Bcl-2的下调。总之，我们的研究结果表明，AFB（1）和ZEA或DON在农产品中共存可能比单独存在更具有肝毒性，这表明需要更好地了解这些毒素的毒理学相互作用以评估健康风险。(C)2015爱思唯尔有限公司版权所有。
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.