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

Abstract

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 retinoic acid receptor. Some observations suggest that the main aromatic retinoid etretinate (Tigason) exerts its therapeutic effect in psoriasis also through an action on the cell membrane. In this paper, we present the results of previously unreleased experiments (when Tigason was still in use) concerning the in vivo and in vitro influence of etretinate on erythrocyte membrane fluidity in psoriatic patients. Erythrocytes from healthy subjects and topically treated psoriatics were chosen as control groups. Membrane fluidity was measured by the electron paramagnetic resonance (EPR) spin-labelling technique. Erythrocytes from psoriatic patients had lower membrane fluidity, a lower antioxidant activity and a greater susceptibility to peroxidation than those from healthy subjects. After treatment with etretinate, a significant increase in erythrocyte membrane fluidity and in antioxidant activity as well as a decrease in lipid peroxidation were observed in erythrocytes from patients. Local therapy of psoriatic lesions had no influence on the improvement in membrane fluidity and antioxidant activity of erythrocytes. Incubation of erythrocytes from healthy controls and topically treated psoriatics with etretinate in vitro confirmed its fluidizing effect on erythrocyte membranes. These data may indicate that two mechanisms lead to an increase in erythrocyte membrane fluidity in psoriatic patients treated with Tigason: the first one, indirect, by improvement of the antioxidant defence system and cell protection against lipid peroxidation, and the second one, by a direct fluidizing effect of etretinate on the erythrocyte membrane.