Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions
Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions
复制标题
DOI：
10.4238/2013.july.24.6
复制
发表时间：
2013-01-01
影响因子：
0.4
通讯作者：
Maistro, E. L.
中科院分区：
文献类型：
--
作者：
Aquino, I.;Tsuboy, M. S. F.;Maistro, E. L.
世界卫生组织推荐的疟疾治疗涉及从青蒿素（一种从黄花蒿中提取的活性化合物）及其一些衍生物（如青蒿琥酯）中提取的药物。考虑到这些化合物对人类细胞的遗传毒性作用缺乏相关数据，本研究的目的是评估青蒿素和青蒿琥酯对培养的人肝细胞肝癌细胞系（HepG2细胞）的细胞毒性和遗传毒性，以及CASP3和SOD1基因的表达。我们对这两种物质的浓度分别为2.5、5、7.5、10和20 μ g/mL，并对基因毒性实验（2.5、5和10 μ g/mL）和基因表达分析（5 μ g/mL）的浓度进行了测定。在用青蒿素和青蒿琥酯处理的细胞中，彗星试验的结果显示，在所有测试浓度下，DNA损伤的细胞数量都有显著的剂量依赖性增加（P < 0.001）。然而，基因表达分析显示CASP3和SOD1的表达没有明显变化。我们的数据显示，尽管青蒿素和青蒿琥酯在培养的HepG2细胞中表现出遗传毒性作用，但它们在测试剂量下并没有显著改变CASP3和SOD1基因的表达。
The malaria treatment recommended by the World Health Organization involves medicines derived from artemisinin, an active compound extracted from the plant Artemisia annua, and some of its derivatives, such as artesunate. Considering the lack of data regarding the genotoxic effects of these compounds in human cells, the objective of this study was to evaluate the cytotoxicity and genotoxicity, and expressions of the CASP3 and SOD1 genes in a cultured human hepatocellular liver carcinoma cell line (HepG2 cells) treated with artemisinin and artesunate. We tested concentrations of 2.5, 5, 7.5, 10, and 20 mu g/mL of both substances with a resazurin cytotoxicity assay, and the concentrations used in the genotoxicity experiments (2.5, 5, and 10 mu g/mL) and gene expression analysis (5 mu g/mL) were determined. The results of the comet assay in cells treated with artemisinin and artesunate showed a significant dose-dependent increase (P < 0.001) in the number of cells with DNA damage at all concentrations tested. However, the gene expression analysis revealed no significant change in expression of CASP3 or SOD1. Our data showed that although artemisinin and artesunate exhibited genotoxic effects in cultured HepG2 cells, they did not significantly alter expression of the CASP3 and SOD1 genes at the doses tested.