Hydroxy-1-aryl-isochromans: protective compounds against lipid peroxidation and cellular nitrosative stress.

Hydroxy-1-aryl-isochromans are a novel class of polyphenolic heterocyclic compounds with potent antioxidative potential. Here we investigated the protective effects of hydroxy-1-aryl-isochroman derivatives against lipid peroxidation and nitrosative stress as a function of their degree of hydroxylation. Measurements of thiobarbituric acid reactive substances (TBARS) in rat brain mitochondria, nitric oxide analysis in microglia cultures, and cell viability analysis were performed. We found that hydroxyl-1-aryl-isochroman derivatives with two, three, and four hydroxyl groups (ISO-2, ISO-3, and ISO-4, respectively) display a higher activity against mitochondrial lipid peroxidation than the corresponding derivative without hydroxyl groups (ISO-0) as well as the reference antioxidant Trolox. However, ISO-0 strongly reduced microglial nitric oxide production, whereas ISO-2 and ISO-4 had a less pronounced effect and ISO-3 was even ineffective. ISO-0 and ISO-3 increased the cell viability of activated microglia, whereas a minor effect of ISO-2 and no significant increase after treatment with ISO-4 could be observed. In conclusion, hydroxy-1-aryl-isochromans exhibit cytoprotective properties, besides their action against reactive oxygen/nitrogen species.