Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.

Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.
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铝和苯并[a]芘协同诱导体外神经元凋亡。

DOI:
10.2131/jts.40.365
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发表时间:
2015-06
期刊:
J Toxicol Sci
影响因子:
--
通讯作者:
牛侨
牛侨
中科院分区:
其他
文献类型:
--
作者:
殷金珠;张勤丽;杨瑾;亢盼;黄建军;牛侨

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环境中有毒有害因素共存,这些因素往往相互作用而产生联合毒性,这是毒理学研究的主要焦点。此外,大量研究表明,铝(Al)和苯并[a]芘(BaP)具有神经毒性,靶向中枢神经系统引起神经元凋亡。由于我们暴露于空气、水、食物甚至药物中的Al和BaP,因此必须检查这些制剂对人体的综合影响。本研究探讨铝和苯并(a)芘共暴露的能力,以加强神经细胞凋亡。新生大鼠原代神经元培养5d后,取同批次生长良好的细胞,分为空白对照组、溶剂对照组(DMSO+S9+麦芽酚)、BaP组(10、40 μmol/L)、Al(mal)3组(50、100、400 μmol/L)以及BaP与Al(mal)3不同组合共暴露组。细胞活力表明10 μM BaP或50 μM Al(mal)3具有轻度毒性,我们选择10 μM BaP+50 μM Al(mal)3进行后续的共暴露实验。透射电镜和荧光倒置显微镜观察发现,共暴露组细胞凋亡的形态学特征明显高于单独暴露组和单独暴露组。细胞凋亡率和caspase-3活性在共暴露组和铝暴露组之间存在显著差异,而BaP暴露组与对照组之间没有显著差异。这些结果表明,铝和苯并(a)芘联合暴露对神经细胞凋亡具有协同作用。
Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 μmol/L), Al (mal)3 groups (50, 100, 400 μmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 μM BaP or 50 μM Al (mal)3 was mildly toxic, and we selected 10 μM BaP+50 μM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis.
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