Lidocaine: a hydroxyl radical scavenger and singlet oxygen quencher.
Lidocaine, a local anaesthetic, has been shown to reduce ventricular arrhythmias associated with myocardial infarction and ischemic myocardial injury and its protective effects has been attributed to its membrane stabilizing properties. Since oxygen radicals are known to be produced during ischemia induced tissue damage, we have investigated the possible antioxidant properties of lidocaine and found that lidocaine does not scavenge O2-. radicals at 1 to 20 mM concentrations. However, lidocaine was found to be a potent scavenger of hydroxyl radicals and singlet oxygen. Hydroxyl radicals were produced in a Fenton type reaction and detected as DMPO-OH adducts by electron paramagnetic resonance spectroscopic techniques. Lidocaine inhibited DMPO-OH adduct formation in a dose dependent manner. The amount of lidocaine needed to cause 50% inhibition of that rate was found to be approximately 80 microM and at 300 microM concentration it virtually eliminated the DMPO-OH adduct formation. The production of OH.-dependent TBA reactive products of deoxyribose was also inhibited by lidocaine in a dose dependent manner. Lidocaine was also found to inhibit the 1O2-dependent 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) formation in a dose dependent manner. 1O2 was produced in a photosensitizing system using Rose Bengal or Methylene Blue as photosensitizers and was detected as TEMP-1O2 adduct by EPR spectroscopy. The amount of lidocaine required to cause 50% inhibition of TEMP-1O2 adduct formation was found to be 500 microM. These results suggest that the protective effect of lidocaine on myocardial injury may, in part, be due to its reactive oxygen scavenging properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Das
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Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24060-0442.
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D003497:Cyclic N-Oxides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D005609:Free Radicals; D008012:Lidocaine / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D008012:Lidocaine; C003959:TEMPO