Investigação do dano oxidativo no DNA de linfócitos humanos tratados in vitro com o antimalárico lumefantrina

• Autor(a) principal: Silva, Andréia Cardoso Mendes Rosa da
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFMT
• Texto Completo: http://ri.ufmt.br/handle/1/3745
• topic: Ensaio cometa; Espécies reativas de oxigênio; Lesões no DNA; Terapias combinadas à base de artemisinina; Genotoxicidade; CNPQ::CIENCIAS DA SAUDE; Comet assay; Reactive oxygen specie; DNA damage; Artemisinin-based combination therapy; Genotoxicity

The artemisinin-based combination therapies (ACTs) have been adopted by the World Health Organization as a strategy to overcome the resistance of the Plasmodium to the most frequently used antimalarials, specially chloroquine. Lumefantrine (LF) plus artemether (AR) is the ACT most frequently used worldwide; however, the genotoxic effects of both drugs are poorly known. Recently, we demonstrated the genotoxicity of the LF to human lymphocytes in vitro due to noncovalent interaction with the DNA minor groove. However, drugs may be genotoxic through different mechanisms, such as increasing the production of reactive oxygen species (ROS) which, in turn, cause DNA base lesions. The aim of this study was to investigate if LF cause oxidative DNA damage to human lymphocytes in vitro. Cultures of human lymphocytes were treated with genotoxic concentrations of LF (60, 80 and 100 g/mL). The oxidative DNA damage was evaluated by the comet assay modified with formamidopyrimidine glycosylase. All tested concentrations increased the oxidative DNA damage (LF60= 11.49 + 4.25; LF80= 16.00 + 5.56; LF100= 28.68 + 7.38) in comparison with untreated cells (DMSO 0,6 % = 3.63 + 1.93. p<0.05). This effect was concentration-dependent. This results showed that the LF increases oxidative DNA damage in human lymphocytes, suggesting that the production of ROS would be an additional mechanism of genotoxicity of LF besides the minor groove DNA binding previously described. Additional investigations will be made in order to verify if LF induces the production of ROS.