Prevention of oxidative injury to cardiac phospholipid by membrane-active "stabilizing agents".

Three lipophilic, membrane-active "stabilizing agents," cepharanthine, chlorpromazine, and trifluoperazine, were found to protect myocardial membrane phospholipid from peroxidative injury. The compounds prevented, in a concentration-dependent manner, the cardiac phospholipid peroxidation which resulted from lipid exposure to superoxide-dependent, iron-promoted oxygen-radical chemistry of the type thought to be a causative factor in ischemic-reperfusion tissue damage. Chlorpromazine's antiperoxidant IC50 (i.e., concentration at which peroxidation was inhibited by 50%) was 180 microM; the antiperoxidant potencies of cepharanthine (IC50 = 90 microM) and trifluoperazine (IC 50 = 100 microM) were some two-fold greater. These agents, at effective antiperoxidant concentrations, did not inhibit the enzymatic superoxide source, xanthine oxidase, scavenge superoxide radical, or act like a chain-breaking antioxidant. The data raise a possibility that the these three membrane-active compounds, as lipophilic anesthetics, may exert antiperoxidant effects by inducing structural changes in the lipid-rich (membrane or liposome) target of free radical attack.