Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy

K.C. Carter, S. Hutchison, A. Boitelle, H.W. Murray, S. Sundar, A. Mullen

Research output: Contribution to journalArticle

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Abstract

Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.

Original languageEnglish
Pages (from-to)747-757
Number of pages10
JournalParasitology
Volume131
Issue number6
Early online date15 Aug 2005
DOIs
Publication statusPublished - 2005

Fingerprint

Antimony Sodium Gluconate
antimony
Leishmania donovani
Antimony
macrophages
Macrophages
sodium
therapeutics
Antimony Potassium Tartrate
Therapeutics
Buthionine Sulfoximine
Respiratory Burst
mice
longitudinal studies
Nitrites
splenocytes
Surface-Active Agents
in vitro studies
nitrites
Hydrogen Peroxide

Keywords

  • Leishmania donovani
  • drug resistance
  • glutathione
  • sodium stibogluconate

Cite this

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title = "Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy",
abstract = "Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.",
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Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy. / Carter, K.C.; Hutchison, S.; Boitelle, A.; Murray, H.W.; Sundar, S.; Mullen, A.

In: Parasitology, Vol. 131, No. 6, 2005, p. 747-757.

Research output: Contribution to journalArticle

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T1 - Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy

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AU - Hutchison, S.

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AU - Murray, H.W.

AU - Sundar, S.

AU - Mullen, A.

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