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Serendipitous findings while researching oxygen free radicals
1Experimental Therapeutics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73170, USA. robert-floyd@omrf.org
Free Radical Biology & Medicine
|May 15, 2009
Summary
Researchers developed sensitive methods to study oxygen free radicals, leading to discoveries in brain injury, DNA damage, viral inactivation, and neuroprotection. These findings have implications for cancer, stroke, and hearing loss treatments.
Area of Science:
- Biomedical Science
- Free Radical Biology
- Oxidative Stress Research
Background:
- Oxygen free radicals play critical roles in various biomedical problems.
- Existing methods for studying free radicals were limited in sensitivity and directness.
Purpose of the Study:
- To develop and apply highly sensitive methods for detecting and quantifying free radicals.
- To investigate the role of free radicals in conditions such as ischemia/reperfusion, DNA damage, viral infections, stroke, and hearing loss.
Main Methods:
- Nitrone free radical spin trapping combined with HPLC-electrochemical detection.
- Use of salicylate as a hydroxyl radical trap.
- Detection of 8-hydroxyl-2-deoxyguanosine in oxidatively damaged DNA.
- Methylene blue (MB) photoinduction studies.
- In vivo studies in experimental stroke models.
Main Results:
- Demonstrated increased hydroxyl radical flux in ischemia/reperfused brain regions.
- First sensitive detection of 8-hydroxyl-2-deoxyguanosine, linking it to cancer development.
- Showed MB photoinduces 8-hydroxyguanine formation and photoinactivates RNA viruses (HIV, West Nile).
- Discovered alpha-phenyl-tert-butylnitrone (PBN) derivatives (e.g., NXY-059) are neuroprotective post-stroke.
- Identified PBN nitrones as having potent anti-cancer activity and preventing noise-induced hearing loss.
Conclusions:
- Advanced free radical detection methods have yielded significant biomedical insights.
- Free radicals are implicated in diverse pathologies, offering therapeutic targets.
- PBN nitrones show promise for treating stroke, cancer, and hearing loss.
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