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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions

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Autor(es):
Aquino, I. [1] ; Tsuboy, M. S. F. [2] ; Marcarini, J. C. [2] ; Mantovani, M. S. [3] ; Perazzo, F. F. [4] ; Maistro, E. L. [5, 1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Estadual Paulista, Inst Biociencias, Programa Posgrad Biol Geral & Aplicada, Botucatu, SP - Brazil
[2] Univ Estadual Paulista, Inst Biociencias, Programa Posgrad Ciencias Biol Biol Celular & Mol, Rio Claro, SP - Brazil
[3] Univ Estadual Londrina, Lab Genet Toxicol, Londrina, PR - Brazil
[4] Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, Diadema, SP - Brazil
[5] Univ Estadual Paulista, Fac Filosofia & Ciencias, Dept Fonoaudiol, Marilia, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Genetics and Molecular Research; v. 12, n. 3, p. 2517-2527, 2013.
Citações Web of Science: 10
Resumo

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. (AU)

Processo FAPESP: 10/07577-3 - Investigação do potencial genotóxico do artesunato, da artemisinina, da 4-hidroxicumarina esculetina: implantação da metodologia de mutagênese in vitro
Beneficiário:Edson Luis Maistro
Linha de fomento: Auxílio à Pesquisa - Regular