Abstract：
:Visceral leishmaniasis is a life-threatening human disease commonly known as kala-azar. Leishmania donovani is the causative agent of this parasitic disease transmitted by the sand fly vector to infect hosts. Triphenyl tin salicylanilide thiosemicarbazone [Ph(3)Sn(OSal.TSCZH)] (TTST) which is an organometallic complex of triphenyl tin has been evaluated to explore possibility to develop a potent chemotherapeutic agent against visceral leishmaniasis. Effect of triphenyl tin complex on growth inhibition and host--parasite interaction were examined both in vitro and in vivo. Release of toxic superoxide radical was measured spectrophotometrically through the formation of blue formazan derived from reduced nitrobluetetrazolium. To understand mode of action of Ph(3)Sn(OSal.TSCZH), superoxide dismutase activity was determined spectrophotometrically by measuring ability of this enzyme to inhibit pyrogallol autoxidation and also by activity staining of the non-denaturing polyacrylamide gels after separating superoxide dismutase. Antileishmanial activity of triphenyl tin complex were found to be effective both in vitro and in vivo at lower concentrations compared to the existing toxic drugs available. IC(50) of Ph(3)Sn(OSal.TSCZH) was calculated as 0.05+/-0.01mg/L. Intracellular survival of the parasite in host macrophages was inhibited by TTST in a dose dependent manner. Parasite burden in spleen was reduced to 87% under TTST treatment (10mg/kg body weight) and under sodium antimony gluconate (20mg/kg body weight) reduced nearly to 65%. Its action as a chemotherapeutic agent is found to be mediated through inhibition of superoxide dismutase and simultaneous release of toxic superoxide radical. We propose that Ph(3) Sn(OSal.TSCZH) may be considered as a prospective candidate to establish a better line of therapeutic process against experimental visceral leishmaniasis.
journal_name
Acta Tropjournal_title
Acta tropicaauthors
Raychaudhury B,Banerjee S,Gupta S,Singh RV,Datta SCdoi
10.1016/j.actatropica.2005.03.008subject
Has Abstractpub_date
2005-07-01 00:00:00pages
1-8issue
1eissn
0001-706Xissn
1873-6254pii
S0001-706X(05)00077-Xjournal_volume
95pub_type
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