Department of Biochemistry and Molecular Biology, University of Bucharest,91-95 Splaiul Independetei, 050095 Bucharest, Romania.
Toxicon. 2011 Jun;57(7-8):1023-32. doi: 10.1016/j.toxicon.2011.04.006. Epub 2011 Apr 29.
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 IC(50) about 7.6 μM. 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 μM 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 μM and decreased in a time-dependent manner for 5 μM. 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.
真菌毒素脱氧雪腐镰刀菌烯醇(DON)是某些食物和饲料的污染物,对哺乳动物细胞具有细胞毒性和遗传毒性。人类胚肾(Hek-293)细胞暴露于 DON 会导致细胞活力呈剂量和时间依赖性下降,IC(50)约为 7.6 μM。研究了 DON 对 Hek-293 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,在某些情况下,细胞附着逐渐丧失。在 2.5 和 5 μM DON 处理 6、12 和 24 h 后评估了这些生化参数。在 6-12 h 期间观察到超氧化物歧化酶活性增加,并且在两种浓度下几乎在实验结束时完全恢复,而过氧化氢酶活性的模式与超氧化物歧化酶相同对于 2.5 μM,并随时间呈下降趋势。暴露后 12 h 记录到谷胱甘肽过氧化物酶和谷胱甘肽还原酶的短暂激活,而对于两种浓度,谷胱甘肽-S-转移酶活性保持不变。NADP(+)依赖性异柠檬酸脱氢酶活性在暴露后 12 h 短暂增加。两种浓度下,caspase 3 表达在暴露 24 h 后保持不变,bcl-2 表达下降。我们的结果表明 Hek-293 细胞抗氧化系统发生了剂量和时间特异性变化,无法有效抵消 DON 暴露的影响。提到了可能由这种 DON 诱导的变化激活的不同类型的细胞死亡。