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The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure

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Abstract

Topoisomerases from trypanosomatids play key functions in the replication and organization of kinetoplast DNA (kDNA). Hence, they are considered as potential targets for anti-parasite drugs. In this paper, the effect of topoisomerase II inhibitors, such as nalidixic acid, novobiocin and etoposide, on the ultrastructure of trypanosomatids that present distinct kDNA arrangements was evaluated. Prokaryotic topoisomerase II inhibitors were more effective on growth arrest and ultrastructure changes than etoposide, a eukaryotic topoisomerase II inhibitor. With the exception of novobiocin, drug concentrations which inhibited cell proliferation also promoted kinetoplast ultrastructure alterations, including the redistribution of topoisomerase II. The data reinforce the concept that prokaryotic topoisomerase II inhibitors may offer greater selectivity in drug therapy of trypanosomatid infections.

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Acknowledgements

The authors are grateful to Dr. Dan S. Ray from University of California, Los Angeles, for kindly providing the antibodies raised against C. fasciculata mitochondrial topo II and Juliana Dutra for technical assistance in obtaining the confocal images. This investigation received financial support from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Universitária José Bonifácio (FUJB) and Ministério da Ciência e Tecnologia—Programa Núcleos de Excelência (PRONEX).

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Authors and Affiliations

  1. Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco G, subsolo, 21949-900, Rio de Janeiro, RJ, Brazil

    Danielle P. Cavalcanti, Wanderley de Souza & Maria Cristina M. Motta

  2. Instituto de Biologia Molecular do Paraná, Curitiba, Paraná, Brazil

    Stênio P. Fragoso & Samuel Goldenberg

  3. Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil

    Stênio P. Fragoso & Samuel Goldenberg

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  1. Danielle P. Cavalcanti
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  2. Stênio P. Fragoso
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  3. Samuel Goldenberg
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  4. Wanderley de Souza
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  5. Maria Cristina M. Motta
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Correspondence to Maria Cristina M. Motta.

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Cavalcanti, D.P., Fragoso, S.P., Goldenberg, S. et al. The effect of topoisomerase II inhibitors on the kinetoplast ultrastructure. Parasitol Res 94, 439–448 (2004). https://doi.org/10.1007/s00436-004-1223-4

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  • DOI: https://doi.org/10.1007/s00436-004-1223-4

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