TY - JOUR
T1 - Efficacy of artemisinin in experimental visceral leishmaniasis
AU - Sen, Rupashree
AU - Ganguly, Sudipto
AU - Saha, Piu
AU - Chatterjee, Mitali
N1 - Funding Information:
Funding: RS and PS are recipients of a Senior Research Fellowship from the Indian Council of Medical Research , Government of India. SG was the recipient of a Senior Research Fellowship from University Grants Commission , Government of India. This work received financial assistance from Indian Council of Medical Research and Dept. of Science & Technology, Govt. of India.
PY - 2010/7
Y1 - 2010/7
N2 - 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 (IC50) ranged from 100μM to 120μM 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.
AB - 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 (IC50) ranged from 100μM to 120μM 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.
KW - Antileishmanial
KW - Artemisinin
KW - Experimental visceral leishmaniasis
KW - Leishmaniasis
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U2 - 10.1016/j.ijantimicag.2010.03.008
DO - 10.1016/j.ijantimicag.2010.03.008
M3 - Article
C2 - 20403680
AN - SCOPUS:77953024390
SN - 0924-8579
VL - 36
SP - 43
EP - 49
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 1
ER -