title: Effect of thioridazine on erythrocytes.
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.
authors.affiliation: Department of Physiology, Eberhard-Karls-University of Tuebingen, Gmelinstr.5, Tuebingen 72076, Germany. florian.lang@uni-tuebingen.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.forename: Paola
authors.initials: P
authors.lastname: Modicano
authors.forename: Markus
authors.initials: M
authors.lastname: Arnold
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Majed
authors.initials: M
authors.lastname: Abed
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D013881:Thioridazine / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014150:Antipsychotic Agents; D013881:Thioridazine; D002118:Calcium