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.
Janero
D R
DR
Department of Pharmacology and Chemotherapy, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Burghardt
B
B
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D002746:Chlorpromazine / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D002746:Chlorpromazine; D007202:Indicators and Reagents; D008081:Liposomes; D010743:Phospholipids; D014268:Trifluoperazine; D014810:Vitamin E; C006947:cepharanthine; D052117:Benzodioxoles