Avaliação do efeito modulador de diferentes estatinas sobre danos ao DNA induzidos pela doxorrubicina em células somáticas de Drosophila melanogaster

• Ano de defesa: 2015
• Autor(a) principal: Orsolin, Priscila Capelari
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Uberlândia; BR; Programa de Pós-graduação em Genética e Bioquímica; Ciências Biológicas; UFU
• Palavras-chave em Português: Estatinas; Efeito modulador; DXR; Smart; Drosophila melanogaster; Doxorrubicina; Statins; Modulatory effect; CNPQ::CIENCIAS BIOLOGICAS::GENETICA
• Link de acesso: https://repositorio.ufu.br/handle/123456789/15765; https://doi.org/10.14393/ufu.te.2015.94

Statins are antilipemics drugs that promote inhibition of HMG-CoA reductase, an essential enzyme in the cholesterol biosynthetic pathway. Besides inhibiting cholesterol synthesis, can also inhibit the formation of other products, such as isoprenoids, which confers additional benefits this class of drugs, among which, antiproliferative, anti-invasive and pro-apoptotic effects. This thesis has been developed in order to assess the mutagenic/recombinogenic effect of three commonly prescribed statins: atorvastatin, rosuvastatin and simvastatin as well as the possible modulatory effects of statins on DNA damage induced by doxorubicin (DXR), an antitumor drug that promotes intercalation with the DNA molecule and produces free radicals. This analysis was performed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. For this analysis, larvae descendants from the standard (ST) cross and the high bioactivation (HB) cross were treated chronically with five concentrations of each statin alone and in combination with DXR (in a co-treatment system). The results revealed no mutagenic/recombinogenic effect for the three statins tested. The analysis of the co-treated descendants (DXR + statins) revealed a modulating effect of statins on damages induced by DXR in D. melanogaster. This modulating effect, however, was different among the tested drugs. Such a response was observed at all concentrations in the descendants of the ST and HB crosses treated with rosuvastatin; only in descendants of the HB cross treated with atorvastatin and especially in descendants of the ST cross treated with simvastatin. These results show that although statins have the same mechanism of action, there are differences in the effectiveness of responses observed for each statin individually. Induction of apoptosis and, primarily, antioxidant activity appear to be the main mechanisms involved in reducing the frequency of mutant spots and consequent modulation of the damage induced by DXR in D. melanogaster.