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Neurophysiological consequences of nitroxide antioxidants
S M Hahn1, D L Lepinski, A M DeLuca
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Canadian Journal of Physiology and Pharmacology
|March 1, 1995
Summary
Nitroxides, used for radioprotection, can cause neurological toxicity. Researchers found Tempol, Tempamine, and Tempo affected guinea pig brain slices, with Tempol being the least toxic.
Area of Science:
- Neuroscience
- Pharmacology
- Radioprotection
Background:
- Nitroxides are potent antioxidant compounds with demonstrated radioprotective capabilities in both in vivo and in vitro settings.
- The clinical application of nitroxides for radioprotection is hindered by dose-limiting toxicities, predominantly manifesting as neurological side effects.
Purpose of the Study:
- To investigate the central nervous system toxicity of three representative nitroxide compounds: Tempol, Tempamine, and Tempo.
- To evaluate the impact of these nitroxides on neuronal excitability in the hippocampus.
Main Methods:
- Electrophysiological recordings were performed on slices of guinea pig hippocampus.
- The effects of varying concentrations of Tempol, Tempamine, and Tempo on neuronal activity, including population spikes and excitatory postsynaptic potentials (EPSPs), were analyzed.
Main Results:
- All three nitroxides modulated neuronal excitability, increasing population spikes and potentiating EPSP-spike coupling.
- High concentrations of Tempo and Tempamine induced repetitive and epileptiform activity, indicating significant neurotoxicity.
- Tempol exhibited the lowest toxicity profile among the tested nitroxides, followed by Tempamine, and then Tempo.
Conclusions:
- Nitroxides exert dose-dependent effects on central nervous system neuronal function.
- Tempol demonstrates a more favorable toxicity profile compared to Tempamine and Tempo for potential therapeutic applications.
- Further research is essential to elucidate the precise mechanisms of nitroxide neurotoxicity and to develop strategies for mitigating these adverse effects.