No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells
No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells
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DOI：
10.1016/s1734-1140(11)70584-9
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Wang, Yitao
中科院分区：
文献类型：
--
作者：
Chen, Xiuping;Zhong, Zhangfeng;Wang, Yitao
细胞内活性氧（ROS）的清除是许多抗氧化剂发挥保护作用的潜在机制之一。姜黄素是一种天然产物，是一种有效的 ROS 清除剂。然而，其ROS清除能力在其细胞保护作用中的作用仍有待阐明。在此，确定了姜黄素对过氧化氢 (H2O2) 和叔丁基过氧化氢诱导的 ROS 形成和 HepG2 细胞损伤的保护作用。 HepG2细胞用姜黄素预处理30分钟，然后用H2O2(500μM)或叔丁基过氧化氢(200μM)处理24小时。姜黄素预处理显着降低了 H2O2 和叔丁基过氧化氢诱导的 ROS 产生，但未能抑制这些化合物的细胞毒性。姜黄素无法逆转 H2O2 引起的线粒体膜电位 (Delta psi m) 降低和 DNA 碎片增加。此外，姜黄素增强H2O2诱导的促凋亡蛋白Bax的表达，并抑制抗凋亡蛋白Bcl-2和Bcl-xL的表达。此外，姜黄素显着降低 p38MAPK 和磷酸-CDC-2 蛋白表达，并增加磷酸-p38MAPK、p42/44MAPK 和磷酸-p42/44MAPK 蛋白表达。这些结果表明，短期预处理和随后较长时间的低浓度姜黄素联合处理对H2O2诱导的HepG2细胞损伤没有明显的保护作用。
Scavenging of intracellular reactive oxygen species (ROS) is one of the potential mechanisms contributing to the protective effects of many antioxidants. Curcumin, a natural product, is an effective ROS scavenger. However, the role of its ROS scavenging ability in its cytoprotective action remains to be clarified. Herein, the protective effects of curcumin on hydrogen peroxide (H2O2)- and tert-butyl hydroperoxide-induced ROS formation and HepG2 cell injury were determined. HepG2 cells were pretreated with curcumin for 30 min and then treated with H2O2 (500 mu M) or tert-butyl hydroperoxide (200 mu M) for 24 h. Curcumin pretreatment dramatically decreased H2O2- and tert-butyl hydroperoxide-induced ROS production, but failed to suppress cytotoxicity of those compounds. H2O2 induced decreases in mitochondrial membrane potential (Delta psi m) and increases in DNA fragmentation could not be reversed by curcumin. Furthermore, curcumin enhanced expression of H2O2-induced pro-apoptotic protein Bax expression and inhibited expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. In addition, curcumin significantly decreased p38MAPK and phospho-CDC-2 protein expression and increased phospho-p38MAPK, p42/44MAPK, and phospho-p42/44MAPK protein expression. These results suggest that short pretreatment and subsequent longer co-treatment of low concentrations of curcumin showed no obvious protective effect on H2O2-induced HepG2 cell injury.