Lipid peroxidation of phosphatidylcholine liposomes depressed by the calcium channel blockers nifedipine and verapamil and by the antiarrhythmic-antihypoxic drug stobadine.
Nifedipine, verapamil and stobadine were tested and compared with butylated hydroxytoluene (BHT) as possible free radical scavengers inhibiting lipid peroxidation in phosphatidylcholine liposomes. Liposomes were peroxidized by incubation in air at 50 degrees C. Verapamil less than nifedipine less than BHT less than stobadine depressed the lipid peroxidation as detected spectroscopically for conjugate diene and thiobarbituric acid product formation. Verapamil and stobadine were tested as OH radical scavengers in a Fenton-type reaction against spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO), as detected by ESR spectroscopy. The tested drugs competed with DMPO in trapping OH radicals, with stobadine being more effective than verapamil. ESR spectra of nifedipine in the incubated liposomes revealed that nifedipine could be involved in free radical reactions in the liposomes leading to nifedipine-stable radical(s) which were immobilized in the membrane. The obtained results suggest that some of the beneficial effects of the studied drugs can be mediated in disease by their ability to scavenge free radicals and by their protective effect on lipid peroxidation.
Ondrias
K
K
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Misík
V
V
Gergel
D
D
Stasko
A
A
D000889:Anti-Arrhythmia Agents; D002243:Carbolines / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008081:Liposomes; D009543:Nifedipine / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002243:Carbolines; D005609:Free Radicals; D008054:Lipid Peroxides; D008081:Liposomes; D010713:Phosphatidylcholines; D014700:Verapamil; D009543:Nifedipine; C100106:dicarbine