Oral Therapy With Sertraline, A Selective Serotonin Reuptake Inhibitor, Shows Activity Against Leishmania donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Oral Therapy With Sertraline, A Selective Serotonin Reuptake Inhibitor, Shows Activity Against Leishmania donovani
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| Creator |
Palit, Partha
Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
This study was executed to investigate the efficacy of oral therapy and preliminary leishmanicidal
mechanism of sertraline, a selective serotonin reuptake inhibitor widely used for the management
of depression, against Leishmania donovani, a causative agent of visceral leishmaniasis (VL).
Methods: The effect of the drug was determined for: (i) direct promastigote killing by inhibition of MTT
reduction and (ii) killing activity against intracellular amastigotes in mouse peritoneal macrophages by
microscopic evaluation of surviving amastigotes in macrophages in Giemsa-stained slides.
Furthermore, the oral therapy of sertraline against established VL in BALB/c mice was evaluated
through estimation of splenic and liver parasite burdens by Leishman Donovan units. Moreover, the
preliminary mechanism of action of the drug against promastigotes was assessed by measuring the
intracellular ATP levels and oxygen consumption of treated cells.
Results: Sertraline killed L. donovani promastigotes and intracellular amastigotes with 50% inhibitory
concentrations (IC50s) of 2.2 and 2.3 mg/L, respectively. The drug was also effective in eliminating
splenic (72%) and liver (70%) parasite loads in infected BALB/c mice through oral therapy. A sertralineinduced
fall in cytoplasmic ATP levels and oxygen consumption rate in promastigotes suggests the
involvement of an apoptosis mode of cell death in the treated parasites.
Conclusions: Sertraline could be a promising pharmacological tool for the oral treatment of VL.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/240/1/JOURNAL_OF_ANTIMICROBIAL_CHEMOTHERAPY%2C_61(_5)%2C2008[86].pdf
Palit, Partha and Ali, Nahid (2008) Oral Therapy With Sertraline, A Selective Serotonin Reuptake Inhibitor, Shows Activity Against Leishmania donovani. Journal of Antimicrobial Chemotherapy, 61 (5). pp. 1120-1124. |
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| Relation |
http://dx.doi.org/10.1093/jac/dkn046
http://www.eprints.iicb.res.in/240/ |
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