Efficacy of artemisinin in experimental visceral leishmaniasis

Abstract Visceral leishmaniasis (VL), caused by the protozoan Leishmania sp., affects 500 000 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 a...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2010-07, Vol.36 (1), p.43-49
Main Authors: Sen, Rupashree, Ganguly, Sudipto, Saha, Piu, Chatterjee, Mitali
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antileishmanial
Antiprotozoal Agents - administration & dosage
Antiprotozoal Agents - pharmacology
Artemisinin
Artemisinins - administration & dosage
Artemisinins - pharmacology
Biological and medical sciences
Disease Models, Animal
Experimental visceral leishmaniasis
Human protozoal diseases
Humans
Infectious Disease
Infectious diseases
Inhibitory Concentration 50
Leishmania
Leishmania donovani - drug effects
Leishmaniasis
Leishmaniasis, Visceral - drug therapy
Leshmaniasis
Macrophages - parasitology
Medical sciences
Mice
Mice, Inbred BALB C
Parasitic diseases
Parasitic Sensitivity Tests
Pharmacology. Drug treatments
Protozoal diseases
Spleen - parasitology
Spleen - pathology
Treatment Outcome
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Summary:Abstract Visceral leishmaniasis (VL), caused by the protozoan Leishmania sp., affects 500 000 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 (IC50 ) ranged from 100 μM to 120 μM 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 (10 mg/kg and 25 mg/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.
ISSN:0924-8579
1872-7913
DOI:10.1016/j.ijantimicag.2010.03.008