Abstract
EVALUATION OF MILTEFOSINE ACTIVITY AGAINST VIABILITY AND DNA INTEGRITY OF LEISHMANIA DONOVANI PROMASTIGOTES IN VITRO

Braa A. Alshakir* and Khawla H. Zghair

ABSTRACT

Visceral leishmaniasis is the most severe disease from all leishmaniasis forms and can be fatal without treatment. Miltefosine was the first oral drug approved in several countries for treatment of visceral and cutaneous leishmaniasis. Regional variations in susceptibility of Leishmania donovani clinical isolates have been recorded to sodium stibogluconate but not other antileishmanial drugs. This study investigates the viability of Leishmania donovani promastigotes using the colorimetric MTT assay and DNA integrity in vitro after exposed to different concentrations of miltefosine in comparison to untreated parasites. The results were expressed as inhibitory concentration IC50. The IC50 of miltefosine drug after 24, 48 and 72 hr was 13.32 μM, 11.73μM and 10.63μM against L. donovani promastigotes respectively. Miltefosine induce apoptosis like death in L. donovani promastigotes, Degradation of DNA was revealed at 11.04, 12.26, 14.72 and 17.17μM after 24 hr, and the clearly degradation was noticed for these concentrations of miltefosine drug after 48 hr ,while the highest concentration of miltefosine (19.62μM) caused completely lysis of DNA after 24hr. Miltefosine in lower concentrations affect L. donovani viability and induce apoptosis like death, thus it might be a promising approach for developing new oral anti- visceral Leishmanial drug.

Keywords: Leishmania donovani, Miltefosine, promastigotes.


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