In vivo and in vitro influence of etretinate on erythrocyte membrane fluidity

The molecular mechanisms underlying the action of synthetic retinoids have been studied intensively, but they are not fully understood yet. It is well known that retinoids exert their effects on gene expression via the retino ic acid receptor. Some observations suggest that the main aromatic retinoid etretinate (Tigason) exerts its therapeutic effect in psoriasis also throu gh an action on the cell membrane. In this paper, we present the results of previously unreleased experiments (when Tigason was still in use) concerni ng the in vivo and in vitro influence of etretinate on erythrocyte membrane fluidity in psoriatic patients. Erythrocytes from healthy subjects and top ically treated psoriatics were chosen as control groups. Membrane fluidity was measured by the electron paramagnetic resonance (EPR) spin-labelling te chnique. Erythrocytes from psoriatic patients had lower membrane fluidity, a lower antioxidant activity and a greater susceptibility to peroxidation t han those from healthy subjects. After treatment with etretinate, a signifi cant increase in erythrocyte membrane fluidity and in antioxidant activity as well as a decrease in lipid peroxidation were observed in erythrocytes f rom patients. Local therapy of psoriatic lesions had no influence on the im provement in membrane fluidity and antioxidant activity of erythrocytes. In cubation of erythrocytes from healthy controls and topically treated psoria tics with etretinate in vitro confirmed its fluidizing effect on erythrocyt e membranes. These data may indicate that two mechanisms lead to an increas e in erythrocyte membrane fluidify in psoriatic patients treated with Tigas on: the first one, indirect, by improvement of the antioxidant defence syst em and cell protection against lipid peroxidation, and the second one, by a direct fluidizing effect of etretinate on the erythrocyte membrane. (C) 20 01 Published by Elsevier Science B.V.