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Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p′-DDT in U937 macrophages

机译:选定的食品植物化学物质降低U937巨噬细胞中TCDD和p,p'-DDT毒性作用的作用

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To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p′-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT–PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT.
机译:为了评估某些食品植物化学物质在降低环境有毒物质2,3,7,8-四氯二苯并-对二恶英(TCDD)和p,p'-DDT(DDT)的毒性作用方面的有效性,我们测试了在逆转U937人巨噬细胞中这些有毒物质的发炎作用中,使用紫杉醇,诺比汀,色骨素和(±)-13-羟基-10-氧代-反式-11-十八碳烯酸(13-HOA)。使用定量RT-PCR作为初始筛选方法,我们确定了蛇骨酮和奥普拉烯对TCDD和DDT在上调COX-2和VEGF mRNA表达中的拮抗作用。通过证明其抑制了TCDD诱导的小鼠MMDD1细胞中COX-2基因表达的激活,证实了佐仑骨对COX-2表达的抑制作用的功能意义。我们在U937巨噬细胞中测试了Aupaptene对DDT诱导的活性氧(ROS)形成的影响,发现auraptene是对抗DDT此作用的强大试剂。为了在细胞水平上确认采鲁骨酮和金刚烷这些作用的重要性,我们评估了它们对完整U937巨噬细胞中TCDD诱导的细胞凋亡抗性的影响,并发现它们能够逆转TCDD的这种作用。总之,在保护U937巨噬细胞免于产生TCDD和DDT的这些细胞毒性作用方面,蛇麻骨和金刚烷被认为是最有效的药物。

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