School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore - 641046, India.
Free Radic Biol Med. 2010 Jul 1;49(1):50-60. doi: 10.1016/j.freeradbiomed.2010.03.016. Epub 2010 Mar 27.
Increasing evidence suggests that oxidative stress is closely linked to toxic responses in cells. The tricothecene mycotoxin, Deoxynivalenol (DON), primarily affects cells of the immune system and the GI tract. DON's cytotoxicity is closely linked to intracellular ROS, and it exerts its toxic effect by a mechanism known as ribotoxic stress response, which drives both cytokine expressions at low dosages and apoptosis at high dosages. Studies to alleviate DON's toxicity are sparsely reported in literature. In the present study, the cytoprotective effect of lutein, was tested in HT-29 cells against DON-induced oxidative stress and cytotoxicity. MTT assay revealed IC(20) values of DON at 250 ng/ml. Pre-treatment of cells with 10 microM lutein resulted in 95% cell viability. Lutein combated DON-induced oxidative stress and downregulated expression of inflammatory genes, NF-kappaB and COX-2. Lutein also prevented DON-induced migration of NF-kappaB into the nucleus, as measured by immunofluorescence. Morphological studies by Electron microscopy and Cell cycle analysis by flow cytometry indicated that lutein prevented DON-induced apoptosis. The results of the present study demonstrate for the first time that lutein exerts a cytoprotective role in DON-induced toxicity.
越来越多的证据表明，氧化应激与细胞中毒反应密切相关。单端孢霉烯族真菌毒素脱氧雪腐镰刀菌烯醇（DON）主要影响免疫系统和胃肠道细胞。DON 的细胞毒性与细胞内 ROS 密切相关，它通过一种称为核糖体毒性应激反应的机制发挥其毒性作用，该机制在低剂量下驱动细胞因子的表达，在高剂量下则诱导细胞凋亡。文献中鲜有关于减轻 DON 毒性的研究。在本研究中，研究了叶黄素在 HT-29 细胞中对 DON 诱导的氧化应激和细胞毒性的保护作用。MTT 检测法显示 DON 的 IC（20）值为 250ng/ml。细胞用 10μM 叶黄素预处理，细胞活力达到 95%。叶黄素对抗 DON 诱导的氧化应激并下调炎症基因 NF-κB 和 COX-2 的表达。叶黄素还通过免疫荧光测定阻止 DON 诱导的 NF-κB 向核内迁移。电子显微镜的形态学研究和流式细胞术的细胞周期分析表明，叶黄素可防止 DON 诱导的细胞凋亡。本研究首次证明叶黄素在 DON 诱导的毒性中发挥细胞保护作用。
