Human cells and cell membrane molecular models are affected in vitro by chlorpromazine.
This study presents evidence that chlorpromazine (CPZ) affects human cells and cell membrane molecular models. Human SH-SY5Y neuroblastoma cells incubated with 0.1 mM CPZ suffered a decrease of cell viability. On the other hand, phase contrast microscopy observations of human erythrocytes indicated that they underwent a morphological alteration as 1 microM CPZ changed their discoid normal shape to stomatocytes, and to hemolysis with 1 mM CPZ. X-ray diffraction experiments performed on dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of the major phospholipids present in the outer and inner sides of the erythrocyte membrane, respectively showed that CPZ disordered the polar head and acyl chain regions of both DMPC and DMPE, where these interactions were stronger with DMPC bilayers. Fluorescence spectroscopy on DMPC LUV at 18 degrees C confirmed these results. In fact, the assays showed that CPZ induced a significant reduction of their generalized polarization (GP) and anisotropy (r) values, indicative of enhanced disorder at the polar head and acyl chain regions of the DMPC lipid bilayer.
Suwalsky
Mario
M
Faculty of Chemical Sciences, University of Concepción, Concepción, Chile. msuwalsk@udec.cl
Villena
Fernando
F
Sotomayor
Carlos P
CP
Bolognin
Silvia
S
Zatta
Paolo
P
D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002746:Chlorpromazine / Q000737:chemistry / Q000633:toxicity*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects*; D020404:Glycerophospholipids / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009447:Neuroblastoma; D013050:Spectrometry, Fluorescence; D018675:Toxicity Tests; D014961:X-Ray Diffraction
C104364:1,2-dimyristoyl-sn-glycero-3-phosphatidylethanol; D020404:Glycerophospholipids; D008051:Lipid Bilayers; D002746:Chlorpromazine; D004134:Dimyristoylphosphatidylcholine