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Avaliação dos efeitos anti-proliferativos de fármacos inibidores de topoisomerases do tipo II em promastigotas de Leishmania infantum
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Authors
Abstract(s)
A Leishmaniose canina é uma doença endémica e de elevada incidência em Portugal. O
arsenal farmacológico disponível não permite a cura parasitológica, causa efeitos tóxicos
graves no organismo e os protocolos terapêuticos são onerosos. De forma a aumentar o leque
de alternativas no combate a este protozoário foram avaliados os efeitos inibitórios das
fluoroquinolonas em promastigotas de Leishmania infantum. Esta família de antibióticos são
inibidores de topoisomerases de tipo II, enzimas fundamentais para o metabolismo dos ácidos
nucleicos bacterianos.
Neste estudo foi analisado, in vitro, o efeito anti-proliferativo de um conjunto de
fluoroquinolonas comerciais (quatro gerações), visando várias concentrações (0,1 μM, 1 μM,
10 μM e 100 μM), em promastigotas de L. infantum. Esta análise foi realizada através de um
ensaio colorimétrico de viabilidade celular e, paralelamente, por observações e contagens ao
microscópio ótico, sendo os resultados confrontados com um controlo positivo (antimoniato
de meglumina). Os resultados obtidos foram também comparados com os resultados obtidos a
partir de culturas de promastigotas não tratados (controlo negativo). Após a análise dos
resultados, as fluoroquinolonas de terceira e quarta geração, particularmente a levofloxacina,
a clinafloxacina e a garenoxacina, foram das fluoroquinolonas estudadas, as que mostraram
maior efeito citotóxico sobre o parasita.
Desta forma, o uso de fluoroquinolonas poderá vir a constituir uma abordagem terapêutica
promissora para a Leishmaniose canina, também por estas apresentarem uma menor
propensão para o desenvolvimento de resistências, uma menor toxicidade e um custo inferior
relativamente aos fármacos atualmente utilizados.
In Portugal, canine Leishmaniosis is an endemic disease with a high incidence. The available drugs do not enable the complete heal, besides being onerous and their inherent toxic effects. In order to broaden the range of alternatives applicable to the treatment of this disease, Leishmania infantum promastigotes were exposed to some commercial fluoroquinolones to establish their cytotoxic effect. Fluoroquinolones are a family of antibiotics that inhibit the action of topoisomerase II in bacteria. These enzymes are essential for nucleic acids metabolism, also in eukaryotes. This study aims to determine the antiproliferative effect of a set of commercial fluoroquinolones, including 1st, 2nd, 3rd and 4th generation, incubating several concentrations (0.1, 1, 10 and 100 μM) on L. infantum promastigotes. The cellular viability was evaluated through a colorimetric MTS assay in comparison to untreated parasites (negative control) and parasites treated with meglumine antimoniate (positive control). At the same time, daily observations and counts at the microscope were carried out. The results demonstrated that fluoroquinolones of third and fourth generation, as levofloxacin, clinafloxacin and garenoxacin, did reveal a strong cytotoxic effect. Therefore, fluoroquinolones can represent an important advantage in the treatment of canine Leishmaniosis, as they are less prone to resistance development, less toxic and less expensive than currently used drugs.
In Portugal, canine Leishmaniosis is an endemic disease with a high incidence. The available drugs do not enable the complete heal, besides being onerous and their inherent toxic effects. In order to broaden the range of alternatives applicable to the treatment of this disease, Leishmania infantum promastigotes were exposed to some commercial fluoroquinolones to establish their cytotoxic effect. Fluoroquinolones are a family of antibiotics that inhibit the action of topoisomerase II in bacteria. These enzymes are essential for nucleic acids metabolism, also in eukaryotes. This study aims to determine the antiproliferative effect of a set of commercial fluoroquinolones, including 1st, 2nd, 3rd and 4th generation, incubating several concentrations (0.1, 1, 10 and 100 μM) on L. infantum promastigotes. The cellular viability was evaluated through a colorimetric MTS assay in comparison to untreated parasites (negative control) and parasites treated with meglumine antimoniate (positive control). At the same time, daily observations and counts at the microscope were carried out. The results demonstrated that fluoroquinolones of third and fourth generation, as levofloxacin, clinafloxacin and garenoxacin, did reveal a strong cytotoxic effect. Therefore, fluoroquinolones can represent an important advantage in the treatment of canine Leishmaniosis, as they are less prone to resistance development, less toxic and less expensive than currently used drugs.
Description
Dissertação de Mestrado Integrado em Medicina Veterinária
Keywords
Leishmania infantum Leishmaniose topoisomerase II fluoroquinolonas Leishmaniosis fluoroquinolones
Pedagogical Context
Citation
Franco, S.M.G. (2013). Avaliação dos efeitos anti-proliferativos de fármacos inibidores de topoisomerases do tipo II em promastigotas de Leishmania infantum. Dissertação de Mestrado. Universidade Técnica de Lisboa, Faculdade de Medicina Veterinária, Lisboa.
Publisher
Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária