To discover the mode of action of alkyl-lysophospholipids in Leishmania donovani, we studied the effects of edelfosine, miltefosine, and ilmofosine on intracellular pH, the parasite's cell cycle, and the induction of apoptosis. The effect of the alkyl-lysophospholipids was combined with that of inhibitors of some pumps and exchange regulators of intracellular pH (Na+/ H+; Cl−/CO−3; and the Na+/K+ ATPase). The effect of the 3 alkyl-lysophospholipids on intracellular pH was indirect; the primary action occurred in the parasite's cell membrane. To determine intracellular pH, we used flow cytometry for the macrophages and axenic amastigotes and spectrofluorometry for the promastigote forms. Apoptosis and the cell cycle were studied by flow cytometry. Treatment of the extracellular promastigote form of L. donovani with the 3 alkyl-lysophospholipids induced death by apoptosis, whereas in the infected cell they caused necrosis rather than apoptosis. Miltefosine and ilmofosine at doses of 38 μM caused G2/M cell cycle inhibition in L. donovani promastigotes.
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October 2006
BIOCHEMISTRY-PHYSIOLOGY|
October 01 2006
ASPECTS OF THE CYTOLOGICAL ACTIVITY OF EDELFOSINE, MILTEFOSINE, AND ILMOFOSINE IN LEISHMANIA DONOVANI
S. Azzouz;
S. Azzouz
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
* Present address: Laboratoire de Parasitologie, Faculté Pharmacie, Université Claude Bernard, Lyon I, 8, avenue Rockefeller, 69373 Lyon Cedex 08, France
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M. Maache;
M. Maache
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
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M. F. Dos Santos;
M. F. Dos Santos
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
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M. E. Sarciron;
M. E. Sarciron
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
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A. F. Petavy;
A. F. Petavy
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
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A. Osuna
A. Osuna
Institute of Biotechnology, Department of Parasitology, University of Granada Campus Fuentenueva 18071, Granada, Spain. aosuna@ugr.es
† To whom correspondence should be addressed
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J Parasitol (2006) 92 (5): 877–883.
Citation
S. Azzouz, M. Maache, M. F. Dos Santos, M. E. Sarciron, A. F. Petavy, A. Osuna; ASPECTS OF THE CYTOLOGICAL ACTIVITY OF EDELFOSINE, MILTEFOSINE, AND ILMOFOSINE IN LEISHMANIA DONOVANI. J Parasitol 1 October 2006; 92 (5): 877–883. doi: https://doi.org/10.1645/GE-632R1.1
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