Free Radical Formation During Ketamine Anesthesia in Rats: A Cautionary Note

• Published in: Free radical biology & medicine 1998-04, Vol.24 (6), p.1002-1006
• Main Authors: Reinke, Lester A, Kotake, Yashige, Moore, Danny R, Nanji, Amin A
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia, General - adverse effects; Animals; Biological oxidations; electron paramagnetic resonance (equivalent to ESR, electron spin resonance); Electron Spin Resonance Spectroscopy; EPR; EPR spectroscopy; Free radicals; Free Radicals - metabolism; hydroxyl radical; Ketamine; Ketamine - adverse effects; Ketamine - metabolism; Male; Microsomes, Liver - metabolism; Nitrogen Oxides - metabolism; OH; POBN; Pyridines; Rats; Rats, Sprague-Dawley; Spin Trapping; α-(4-pyridyl 1-oxide)- N- t-butylnitrone
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(97)00393-6

Ketamine is a useful anesthetic agent with good analgesic properties; however, when ketamine was used to anesthetize rats for spin trapping studies of alcohol-induced free radicals, liver extracts contained a strong electron paramagnetic resonance (EPR) signal of a novel radical. The same EPR signal was observed in liver extracts when rats which had not received alcohol were anesthetized with ketamine. When ketamine was added to liver microsomes and NADPH, a nitroxide radical derived from ketamine could be detected in organic extracts. When the spin trapping agent POBN was also added, microsomes produced both a ketamine nitroxide radical and a spin adduct. Similar results were obtained during ketamine oxidation by hydrogen peroxide in a tungstate-catalyzed reaction, or in a Fenton reaction system. The data suggest that the secondary amine group of ketamine can be oxidized to a stable nitroxide which produces an EPR spectrum in the absence of a spin trapping agent. The POBN spin adduct detected may be from a carbon-centered radical in the cyclohexanone ring of ketamine. Because several types of radicals can be formed from ketamine, this agent may not be appropriate as an anesthetic for many types of in vivo spin trapping experiments.