Effects of salicylic acid derivatives on red blood cell membranes

Salicylamide, sodium salicylate and acetylsalicylic acid are salicylic acid derivates. They differ in their substitution on the benzene ring and may h ave different effects on membranes. Red blood cells were used as a prototyp ical cellular system regarding drug mediated plasma bilayer effects. Establ ished photometric methods sensing tiny changes of red blood cell morphology at rest (red blood ceh shape) and at very low shear forces (red blood cell stiffness, red blood cell relaxation time) were applied. The derivative in duced effects were detected in a time- and dose-dependent manner. Salicylam ide induced a most pronounced echinocytic shape at 5 mM. The shape effect w as smaller above as well as below 5 mM. Sodium salicylate induced echinocyt es with increasing concentrations showing a saturation above 10 mM. In cont rast, the shape was not affected by acetylsalicylic acid. All shape changes occurred within 2 min, and were reversible. The above tendencies were in p arallel to a slight red blood cell stiffening. The relaxation time continuo usly increased with increasing concentrations in both salicylamide and sodi um salicylate, with salicylamide always acting stronger. Acetylsalicylic ac id again showed no effect. We hypothesize that the observed effects of sodi um salicylate and salicylamide are due to their phenolic character mediatin g a molecular hydrophobicity. According to the bilayer couple hypothesis th is would lead to an insertion into the red blood cells outer plasma bilayer leaflet. The extension induced here would cause a positive membrane bendin g leading to echinocytic shapes and the observed loss of red blood cell flu idity. In contrast, the hydrophilic aspirin would penetrate and thus not af fect the red blood cell plasma membrane.