Background:

Miltefosine, an alkylphosphocholine drug with antiparasite, antibacterial, antifungal and anineoplastic potency, is the only oral drug that can be used to treat visceral and cutaneous leishmaniasis [Dorlo et al. 2012]. The effect of miltefosine is at least partially due to triggering of apoptosis. Mechanisms involved in miltefosine induced apoptosis include mitochondria. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Eryptosis may be triggered following increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). The present study explored, whether miltefosine elicits eryptosis.

Methods:

Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, hemolysis from hemoglobin release, [Ca²⁺]_i from Fluo3-fluorescence.

Results:

A 48 h exposure to miltefosine (= 2 µg/ml) was followed by a significant decrease of forward scatter and significant increase of annexin-V-binding. The effect was paralleled by a significant increase of [Ca²⁺]_i. The annexin-V-binding following miltefosine treatment was significantly blunted but not abrogated in the nominal absence of extracellular Ca²⁺.

Conclusions:

Miltefosine stimulates eryptosis, an effect at least partially due to stimulation of Ca²⁺ entry.