期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 36, 期 1, 页码 43-49出版社
ELSEVIER
DOI: 10.1016/j.ijantimicag.2010.03.008
关键词
Antileishmanial; Artemisinin; Experimental visceral leishmaniasis; Leishmaniasis
资金
- Indian Council of Medical Research, Government of India
- University Grants Commission, Government of India
- Indian Council of Medical Research and Dept. of Science & Technology, Govt. of India
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 mu M to 120 mu M 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. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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