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1

Department of Physiology, Eberhard-Karls-University of Tuebingen, Gmelinstr.5, Tuebingen 72076, Germany

2

Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno dAlcontres, 31, S. Agata-Messina 98166, Italy



These authors contributed equally to this work.





*

Author to whom correspondence should be addressed.



Abstract Background: Thioridazine, a neuroleptic phenothiazine with antimicrobial efficacy is known to trigger anemia. At least in theory, the anemia could result from stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and by phospholipid scrambling of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-concentration Ca2+i and activation of p38 kinase. The present study explored, whether thioridazine elicits eryptosis. Methods: Ca2+i has been estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, and hemolysis from hemoglobin release. Results: A 48 hours exposure to thioridazine was followed by a significant increase of Ca2+i 30 µM, decrease of forward scatter 30 µM, and increase of annexin-V-binding ≥12 µM. Nominal absence of extracellular Ca2+ and p38 kinase inhibitor SB203580 2 µM significantly blunted but did not abolish annexin-V-binding following thioridazine exposure. Conclusions: Thioridazine stimulates eryptosis, an effect in part due to entry of extracellular Ca2+ and activation of p38 kinase. View Full-Text

Keywords: phosphatidylserine; thioridazine; calcium; cell volume; eryptosis phosphatidylserine; thioridazine; calcium; cell volume; eryptosis





Author: Elisabeth Lang 1,†, Paola Modicano 1,2,†, Markus Arnold 1, Rosi Bissinger 1, Caterina Faggio 2, Majed Abed 1 and Florian Lang 1,*

Source: http://mdpi.com/



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