Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 747-757 |
| Number of pages | 10 |
| Journal | Parasitology |
| Volume | 131 |
| Issue number | 6 |
| Early online date | 15 Aug 2005 |
| DOIs | |
| Publication status | Published - 2005 |
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Keywords
- Leishmania donovani
- drug resistance
- glutathione
- sodium stibogluconate
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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 journal › Article
TY - JOUR
T1 - Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy
AU - Carter, K.C.
AU - Hutchison, S.
AU - Boitelle, A.
AU - Murray, H.W.
AU - Sundar, S.
AU - Mullen, A.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Leishmania donovani
KW - drug resistance
KW - glutathione
KW - sodium stibogluconate
UR - http://dx.doi.org/10.1017/S0031182005008486
U2 - 10.1017/S0031182005008486
DO - 10.1017/S0031182005008486
M3 - Article
VL - 131
SP - 747
EP - 757
JO - Parasitology
JF - Parasitology
SN - 0031-1820
IS - 6
ER -