Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-gamma to IL-10 ratio.

Abstract

We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb(R)) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.

• Authors: Arun Kumar Haldar, Subha Banerjee, Kshudiram Naskar, Diganta Kalita, Nashreen S Islam, Syamal Roy
• Journal: Experimental parasitology (Exp Parasitol) Vol. 122 Issue 2 Pg. 145-54 (Jun 2009) ISSN: 1090-2449 [Electronic] United States
• PMID: 19422069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiprotozoal Agents
• Drug Combinations
• Peroxides
• diperoxovanadate
• Superoxides
• Interleukin-10
• Nitric Oxide
• Vanadates
• Interferon-gamma
• Antimony Sodium Gluconate

Topics

• Animals
• Antimony Sodium Gluconate (administration & dosage, toxicity)
• Antiprotozoal Agents (administration & dosage, chemistry, toxicity)
• Ascitic Fluid (cytology, parasitology)
• Cell Survival (drug effects)
• Cricetinae
• Drug Combinations
• Drug Resistance
• Interferon-gamma (biosynthesis, drug effects)
• Interleukin-10 (biosynthesis)
• Leishmania donovani (drug effects, immunology)
• Leishmaniasis, Visceral (drug therapy, immunology, parasitology)
• Liver (parasitology)
• Mesocricetus
• Mice
• Mice, Inbred BALB C
• Nitric Oxide (biosynthesis)
• Peroxides (administration & dosage, chemistry, toxicity)
• Spleen (parasitology)
• Superoxides (metabolism)
• T-Lymphocytes (drug effects, immunology)
• Vanadates (administration & dosage, chemistry, toxicity)