Aquino I, Tsuboy M S F, Marcarini J C, Mantovani M S, Perazzo F F, Maistro E L
Programa de Pós-Graduação em Biologia Geral e Aplicada, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brasil.
Genet Mol Res. 2013 Jul 24;12(3):2517-27. doi: 10.4238/2013.July.24.6.
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 μg/mL of both substances with a resazurin cytotoxicity assay, and the concentrations used in the genotoxicity experiments (2.5, 5, and 10 μg/mL) and gene expression analysis (5 μg/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.
世界卫生组织推荐的疟疾治疗方法涉及源自青蒿素（一种从植物黄花蒿中提取的活性化合物）及其一些衍生物（如青蒿琥酯）的药物。鉴于缺乏关于这些化合物对人类细胞遗传毒性作用的数据，本研究的目的是评估青蒿素和青蒿琥酯处理的人肝癌细胞系（HepG2细胞）中细胞毒性、遗传毒性以及CASP3和SOD1基因的表达。我们使用刃天青细胞毒性试验测试了两种物质2.5、5、7.5、10和20μg/mL的浓度，并确定了遗传毒性实验（2.5、5和10μg/mL）和基因表达分析（5μg/mL）中使用的浓度。青蒿素和青蒿琥酯处理的细胞彗星试验结果显示，在所有测试浓度下，DNA受损细胞数量均呈显著剂量依赖性增加（P < 0.001）。然而，基因表达分析显示CASP3或SOD1的表达没有显著变化。我们的数据表明，虽然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，但在所测试的剂量下，它们并未显著改变CASP3和SOD1基因的表达。
