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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dc.contributor.authorAquino, Ivani
dc.contributor.authorTsuboy, Marcela Stefanini Ferreira
dc.contributor.authorMarcarini, Juliana Cristina
dc.contributor.authorMantovani, Mário Sérgio
dc.contributor.authorPerazzo, Fábio Ferreira [UNIFESP]
dc.contributor.authorMaistro, Edson Luis
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniv Estadual Paulista
dc.contributor.institutionUniversidade Estadual de Londrina (UEL)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:30:58Z
dc.date.available2016-01-24T14:30:58Z
dc.date.issued2013-01-01
dc.description.abstractThe 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.en
dc.description.affiliationUniv Estadual Paulista, Inst Biociencias, Programa Posgrad Biol Geral & Aplicada, Botucatu, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Inst Biociencias, Programa Posgrad Ciencias Biol Biol Celular & Mol, Rio Claro, SP, Brazil
dc.description.affiliationUniv Estadual Londrina, Lab Genet Toxicol, Londrina, PR, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Filosofia & Ciencias, Dept Fonoaudiol, Marilia, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDCNPq: 306544/2006-7
dc.description.sponsorshipIDFAPESP: 2010/07577-3
dc.format.extent2517-2527
dc.identifierhttp://dx.doi.org/10.4238/2013.July.24.6
dc.identifier.citationGenetics and Molecular Research. Ribeirao Preto: Funpec-editora, v. 12, n. 3, p. 2517-2527, 2013.
dc.identifier.doi10.4238/2013.July.24.6
dc.identifier.issn1676-5680
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35751
dc.identifier.wosWOS:000331717400035
dc.language.isoeng
dc.publisherFunpec-editora
dc.relation.ispartofGenetics and Molecular Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectArtemisininen
dc.subjectArtesunateen
dc.subjectHepG2 cellsen
dc.subjectGene expressionen
dc.subjectComet assayen
dc.subjectCASP3 and SOD1 genesen
dc.titleGenotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressionsen
dc.typeinfo:eu-repo/semantics/article
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