title: Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions.
abstract: 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.
authors: Programa de Pós-Graduação em Biologia Geral e Aplicada, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brasil.
authors: I
authors: I
authors: Aquino
authors: M S F
authors: MS
authors: Tsuboy
authors: J C
authors: JC
authors: Marcarini
authors: M S
authors: MS
authors: Mantovani
authors: F F
authors: FF
authors: Perazzo
authors: E L
authors: EL
authors: Maistro
mesh_terms: D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D037621:Artemisinins / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D000077332:Artesunate; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D007783:Lactones; C000606290:SOD1 protein, human; D000077332:Artesunate; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C505407:CASP3 protein, human; D053148:Caspase 3; C075875:artemisin