Inhibition by aminosalicylates of phosphatidic acid formation induced by superoxide, calcium or spermine in enterocyte mitochondria.

Inflammation is associated with oxidative stress and altered cellular calcium homeostasis. Our earlier studies have shown that, increased phosphatidic acid (PA) formation occurred in enterocyte mitochondria when exposed to superoxide, divalent metal ions or polyamines resulting in altered lipid composition. Since aminosalicylates are the drug of choice for gut inflammation, we have tested the effect of aminosalicylates on PA formation by enterocyte mitochondria. When stimulated by superoxide, Ca2+ or spermine, phosphatidyleth-anolamine (PE) degradation and PA formation occurred in enterocyte mitochondria which can be inhibited by aminosalicylates. The inhibition was 50-60% at 0.5-mM concentration and at 1- or 2-mM final concentration, complete inhibition was observed. Both 5-aminosalicylate (5-ASA) and 4-aminosalicylate (4-ASA) showed similar effects. The stimulation of PA formation by calcium or spermine was not due to increased generation of superoxide by mitochondria which was confirmed by measurement of superoxide production by the mitochondria. These studies suggest that in addition to other cellular effects, aminosalicylates may prevent the enterocyte mitochondrial damage by inhibition of PA formation and PE degradation and alteration of mitochondrial lipid composition.