Atividade tóxica e genotóxica induzida por combinações de antirretrovirais em Drosophila melanogaster e camundongos Mus musculus
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2016-11-07
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Universidade Federal de Goiás
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As result of several mutations of HIV and failures resulting in treatments with only one medicine, it became critical to use a combination of two or more antiretrovirals in AIDS treatment protocols. So, the investigations that were carried out in this research were concentrated in the evaluation of the effects related with cytotoxicity and genotoxicity of Efavirenz (EFV) e Tenofovir (TDF) as isolated and in combination with Combivir® (AZT+3TC) and Lamivudina (3TC). For this, three test systems were used: (i) the Comet assay in Drosophila and mouse bone marrow in order to determine the genotoxic effects of the drugs tested by the DNA strand breaks; (ii) the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, that evaluates the toxic, mutagenic and recombinogenic activity of the compounds and (iii) the Micronucleus Test (MN) in mouse bone marrow, that detects aneugenic and clastogenic effects of agents. The results demonstrated that EFV was toxic at high concentrations and did not show induction of mutagenic and/or recombinogenic events. Inversely, Combivir and Combivir+EFV showed no lethal dose 70 (LD 70) in the concentrations used for genotoxic analysis, but induced mutagenic and/or recombinogenic effects in all tested concentrations, with prevalence of recombinogenic events. The antiretrovirals TDF, 3TC and TDF + 3TC were not toxic, but were gentoxic in all tested concentrations, with a prevalence of recombinogenicity. All of the isolated and combined compounds were positive in the Comet-assay with D. melanogaster. However, the two combinations were negative in the Comet-assay with mouse bone marrow. Combivir+EFV induced micronuclei (MN) in 24 and 48 hours. TDF+3TC induced MN only in 24 hours. Based on these results, we expect to expand the knowledge about the toxic and genotoxic activities of these combinations and to provide support for the development of new studies in AIDS treatment protocols.
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MORAES FILHO, A. V. Atividade tóxica e genotóxica induzida por combinações de antirretrovirais em Drosophila melanogaster e camundongos Mus musculus. 2016. 122 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2016.