Influence of the retinoid acitretin on erythrocyte microrheology in vitro.
OBJECTIVE
To determine in vitro changes in the microrheology of red blood cells (RBCs) treated with acitretin (Ro 10-1670).


METHODS
Venous blood samples were obtained from 27 healthy donors. Washed erythrocytes (5 x 10(6) cells/ml) were incubated for 30 min at 37 degrees C in solutions of low (25 ng/ml) and high (400 ng/ml) acitretin concentration. The whole red cell deformability was measured using osmotic gradient ektacytometry. To assess the contribution of factors influencing changes in red cell deformability, the biophysical state of the phospholipid bilayer was determined using the cation osmotic hemolysis technique (COH) and the internal viscosity using electron paramagnetic resonance (EPR) spectroscopy.


RESULTS
Osmotic deformability studies revealed that cells treated with acitretin at low concentration deformed almost normally in isotonic medium, but RBCs incubated with high acitretin concentration showed distinct loss of deformation. However, in hypotonic medium, cell deformability was reduced to abnormally low values and this change was most marked with high acitretin concentration. CHO measurements showed that incubation of red cells at low acitretin concentration caused a significant increase in hemolysis at ionic strengths from 123.2 - 154.0 mmol/1 NaCl in relation to the control (p < 0.001). A high concentration of acitretin caused a significant increase in COH with high ionic strengths in the range 107.8 - 154.0 mmol/l NaCl (p < 0.001) and at low ionic strengths in the range 15.4 mmol/l NaCl (p < 0.05). The measurement of RBC intracellular microviscosity showed no statistically significant differences between control (6.22+/-0.22 cP) and acitretin-treated (6.29+/-0.25 cP) cells.


CONCLUSIONS
The data show that acitretin, even at low concentration, is capable of inducing the reduction of red cell deformability. A reduced tendency of acitretin-treated RBCs to deform might result from the ability of acitretin to perturb the cell shape and membrane viscoelastic properties.
Górnicki
A
A
Department of Biophysics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland. agor@cm.umk.pl
D017255:Acitretin / Q000494:pharmacology*; D000328:Adult; D001800:Blood Specimen Collection; D004305:Dose-Response Relationship, Drug; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects; D018056:Hemorheology / Q000379:methods*; D006801:Humans; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D007641:Keratolytic Agents / Q000494:pharmacology; D044085:Microfluidics / Q000379:methods; D009994:Osmolar Concentration; D012176:Retinoids / Q000494:pharmacology; D012965:Sodium Chloride / Q000737:chemistry / Q000494:pharmacology; D013048:Specimen Handling / Q000379:methods
D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D007641:Keratolytic Agents; D012176:Retinoids; D012965:Sodium Chloride; D017255:Acitretin