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.
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.
Department of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, West Bengal 700 032, India.
Arun Kumar
AK
Haldar
Subha
S
Banerjee
Kshudiram
K
Naskar
Diganta
D
Kalita
Nashreen S
NS
Islam
Syamal
S
Roy
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage* / Q000633:toxicity; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001202:Ascitic Fluid / Q000166:cytology / Q000469:parasitology; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004338:Drug Combinations; D004351:Drug Resistance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000187:drug effects* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D010545:Peroxides / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D013154:Spleen / Q000469:parasitology; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014638:Vanadates / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity
D000981:Antiprotozoal Agents; D004338:Drug Combinations; D010545:Peroxides; C091767:diperoxovanadate; D013481:Superoxides; D016753:Interleukin-10; D009569:Nitric Oxide; D014638:Vanadates; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate