Antiarrhythmic agents. Scavengers of hydroxyl radicals and inhibitors of NADPH-dependent lipid peroxidation in bovine lung microsomes.
Antiarrhythmic drugs, e.g. lidocaine, quinidine, and procainamide have been suggested as a means of reducing myocardial damage. The mode of action of these drugs have been attributed to their "membrane-stabilizing" properties. However, as tissue ischemia reperfusion is reported to generate toxic species of oxygen, we investigated the oxygen radical scavenging properties of these drugs and their effect on NADPH-dependent lipid peroxidation. These antiarrhythmic drugs are found to be ineffective as superoxide radical scavengers but are potent scavengers of hydroxyl radical with rate constants of 1.8 x 10(10) M-1 s-1, 1.61 x 10(10) M-1 s-1, and 1.45 x 10(10) M-1 s-1 for quinidine, lidocaine and procainamide, respectively, as determined by deoxyribose assay. In EPR study, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, lidocaine, quinidine, and procainamide caused a dose-dependent inhibition of DMPO-OH adduct formation. These drugs also caused a dose-dependent inhibition of NADPH-dependent lipid peroxidation when lung microsomes were incubated with NADPH in presence of Fe(3+)-ADP. We propose that the antiarrhythmic agents exert their beneficial effects, in part, by their ability to scavenge toxic species of oxygen and by reducing membrane lipid peroxidation.
Das
K C
KC
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24060-0442.
Misra
H P
HP
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002417:Cattle; D005609:Free Radicals; D006878:Hydroxides / Q000737:chemistry; D008012:Lidocaine / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry; D011342:Procainamide / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D005609:Free Radicals; D006878:Hydroxides; D008054:Lipid Peroxides; D008012:Lidocaine; D009251:NADPH-Ferrihemoprotein Reductase; D011802:Quinidine; D011342:Procainamide; D010100:Oxygen