Eficacia y toxicidad de los antimoniales pentavalentes (Glucantime y Pentostam) en un modelo animal de leishmaniasis cutánea americana: aplicación de la luminometría.

Translated title of the contribution: Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application

Hector Hernán Henao, Yaneth Osorio, Nancy Gore Saravia, Arlen Gómez, Bruno Travi

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The pentavalent antimonial compounds Glucantime and Pentostam are the first line drugs used in anti-Leishmania treatment. However, no in vivo studies have compared the efficacy and toxicity of these drugs where host variability has been controlled. Biochemical studies of Leishmania have detected differences between the two drugs with regard to DNA topoisomerase I inhibition, a phenomenon that possibly impacts treatment efficacy. To evaluate the clinical efficacy, hamsters were infected intradermally in the right hind foot with 10(6) promastigotes of a wild type or luciferase-transfected Leishmania panamensis. At three weeks post-inoculation, the animals were treated intramuscularly with either Glucantime or Pentostam (30, 60 or 120 mg SbV/kg per day for 20 days). To evaluate parasitological efficacy a luminometry assay was standardized for quantitation of amastigotes in hamster tissues. To evaluate toxicity, hamsters were treated intramuscularly with Glucantime or Pentostam (120, 160 or 240 mg SbV/kg per day for 20 days). Animals inoculated with either of the parasite strains and treated with either drug, showed a similar rate of lesion reduction, as compared to untreated controls (p<0.01). Parasite burden was also comparable, and no significant differences were found in the cure rate. No renal or hepatic alterations occurred as evidenced by normal serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and amylase. Hamsters treated with 120 mg SbV/kg per day for 20 days or higher doses of Pentostam showed macro- and microscopic signs of inflammation at the site of injection. These effects were absent in the animals treated with Glucantime. The results confirmed clinical observations regarding the similar efficacy of the two drugs, as well as the higher local toxicity of Pentostam.

Translated title of the contributionEfficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application
Original languageSpanish
Pages (from-to)393-402
Number of pages10
JournalBiomédica : revista del Instituto Nacional de Salud
Volume24
Issue number4
DOIs
StatePublished - Dec 2004
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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