The Effects of Salicylic and Acetylsalicylic Acids on Mitochondrial and Erythrocyte Membranes

In order to further clarify the mechanisms of pharmacological effects of salicylic and acetylsalicylic acids, the interactions of these acids with mitochondrial and erythrocyte membranes were studied and the role of calcium ions/protons in the effects of salicylates was evaluated. Salicylic acid and, to a lesser extent, acetylsalicylic acid at concentrations of 0.5–2.0 mM effectively inhibited the respiratory activity of isolated rat liver mitochondria by uncoupling respiration and phosphorylation processes, induced depolarization of the mitochondrial membrane and potentiated Ca2+-stimulated formation of mitochondrial permeability transition pore in EGTA-free media. Cyclosporine A and ruthenium red partially inhibited the mitochondrial pore opening process induced by salicylic and acetylsalicylic acids both in the absence and in the presence of Ca2+ ions. Salicylic acid (180–360 μM) significantly accelerated proton-induced lysis (at pH 3.2) of human erythrocytes and caused hyperpolarization of erythrocyte membranes (at pH 5.5, but not at pH 7.4), probably as a result of proton transfer into the cytoplasm of the cell. Thus, salicylic and acetylsalicylic acids interact with mitochondrial and plasma membranes, act as effective proton/Ca2+ ionophores, and stimulate the mitochondrial calcium uniporter.