Efficacy of artemisinin in experimental visceral leishmaniasis.
Visceral leishmaniasis (VL), caused by the protozoan Leishmania sp., affects 500000 people annually, with the Indian subcontinent contributing a significant proportion of these cases. Emerging refractoriness to conventional antimony therapy has emphasised the need for safer yet effective antileishmanial drugs. Artemisinin, a widely used antimalarial, demonstrated anti-promastigote activity and the 50% inhibitory concentration (IC(50)) ranged from 100 microM to 120 microM irrespective of Leishmania species studied. Leishmania donovani-infected macrophages demonstrated decreased production of nitrite as well as mRNA expression of inducible nitric oxide synthase, which was normalised by artemisinin, indicating that it exerted both a direct parasiticidal activity as well as inducing a host protective response. Furthermore, in a BALB/c model of VL, orally administered artemisinin (10mg/kg and 25mg/kg body weight) effectively reduced both splenic weight and parasite burden, which was accompanied by a restoration of Th1 cytokines (interferon-gamma and interleukin-2). Taken together, these findings have delineated the therapeutic potential of artemisinin in experimental VL.
Sen
Rupashree
R
Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya Jagadish Chandra Bose Road, Kolkata 700 020, West Bengal, India.
Ganguly
Sudipto
S
Saha
Piu
P
Chatterjee
Mitali
M
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D037621:Artemisinins / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D037621:Artemisinins; C031327:artemisinin