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

Author Aquino, Ivani Google Scholar
Tsuboy, Marcela Stefanini Ferreira Google Scholar
Marcarini, Juliana Cristina Google Scholar
Mantovani, Mário Sérgio Google Scholar
Perazzo, Fábio Ferreira Autor UNIFESP Google Scholar
Maistro, Edson Luis Google Scholar
Institution Universidade de São Paulo (USP)
Univ Estadual Paulista
Universidade Estadual de Londrina (UEL)
Universidade Federal de São Paulo (UNIFESP)
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 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.
Keywords Artemisinin
Artesunate
HepG2 cells
Gene expression
Comet assay
CASP3 and SOD1 genes
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number CNPq: 306544/2006-7
FAPESP: 2010/07577-3
Date 2013-01-01
Published in Genetics and Molecular Research. Ribeirao Preto: Funpec-editora, v. 12, n. 3, p. 2517-2527, 2013.
ISSN 1676-5680 (Sherpa/Romeo, impact factor)
Publisher Funpec-editora
Extent 2517-2527
Origin http://dx.doi.org/10.4238/2013.July.24.6
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000331717400035
URI http://repositorio.unifesp.br/handle/11600/35751

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