Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells

Adapted response of the antioxidant defense system to oxidative stress induced by deoxynivalenol in Hek-293 cells
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DOI:
10.1016/j.toxicon.2011.04.006
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发表时间:
2011-06-01
期刊:
影响因子:
2.8
通讯作者:
Dinischiotu, Anca
Dinischiotu, Anca
中科院分区:
医学4区
文献类型:
--
作者:
Dinu, Diana;Bodea, Gabriela Oana;Dinischiotu, Anca

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真菌毒素脱氧雪腐镰刀菌烯醇(DON)是某些食品和饲料的污染物,对大肠杆菌细胞具有细胞毒性和遗传毒性。人胚肾(Hek-293)细胞暴露于DON导致细胞活力的剂量和时间依赖性降低,IC 50约为7.6 μ M。观察DON对Hek-293细胞形态、活性氧、脂质过氧化和抗氧化系统以及caspase 3和bcl-2表达的影响。细胞变圆,有些细胞逐渐丧失细胞附着。在用2.5和5 μ M DON处理6、12和24小时后评估这些生化参数。超氧化物歧化酶活性在6-12小时的时间间隔内增加,并且在实验结束时几乎完全恢复,而过氧化氢酶活性的曲线与2.5 μ M的超氧化物歧化酶相同,并且在5 μ M时以时间依赖性的方式下降。谷胱甘肽过氧化物酶和谷胱甘肽还原酶的暂时激活记录在12小时后曝光,而谷胱甘肽-S-转移酶的活性是不变的两个浓度。NADP(+)依赖的异柠檬酸脱氢酶活性在暴露后12 h出现一过性升高。两种浓度染毒24 h后,caspase 3表达无明显变化,bcl-2表达下降。结果表明,Hek-293细胞抗氧化系统的变化具有剂量和时间特异性,不能有效地抵消DON暴露的影响。不同类型的细胞死亡,可以激活这种DON诱导的变化提到。(C)2011爱思唯尔有限公司保留所有权利。
The mycotoxin deoxynivalenol (DON), a contaminant of certain foods and feeds, is cytotoxic and genotoxic to mammalians cells. Exposure of human embryonic kidney (Hek-293) cells to DON led to a dose- and time-dependent decrease in cell viability, with an IC50 about 7.6 mu M. The DON effects on Hek-293 morphology, reactive oxygen species, lipid peroxidation and antioxidative system and caspase 3 and bcl-2 expression were studied. Cells became round and in some are progressive loss of cell attachment appeared. These biochemical parameters were assessed after 6,12 and 24 h of treatment with 2.5 and 5 mu M DON. An increase in superoxide dismutase activity within the interval 6-12 h and almost complete recovery by the end of experiment for both concentrations was observed, whereas the profile of catalase activity was the same with the superoxide dismutase one for 2.5 mu M and decreased in a time-dependent manner for 5 mu M. A temporary activation of glutathione peroxidase and glutathione reductase was recorded at 12 h post-exposure, while the glutathione-S-transferase activity was unchanged for both concentrations. The NADP(+)-dependent isocitrate dehydrogenase activity showed a transient increase at the 12 h post-exposure. The caspase 3 expression remained unchanged and the bcl-2 one decreased after 24 h of exposure for the two concentrations. Our results showed the dose- and time specific changes in the antioxidants system of Hek-293 cells, which could not counteract efficiently the effects DON exposure. The different types of cell death which could be activated by this DON induced changes are mentioned. (C) 2011 Elsevier Ltd. All rights reserved.