Biomarkers of Oxidative Stress Study

Free Radical Metabolism Group

Many techniques currently exist that potentially allow the measurement of the oxidative stress status in animal models and humans; the techniques are as diverse as blood tests for oxidized lipids, volatile hydrocarbons in breath and oxidized DNA bases in urine. To evaluate the available methodology for measuring oxidative stress with potential application to human studies, the Free Radical Metabolism Group has taken the lead in organizing the first nationwide multi-laboratory comprehensive comparative study for determining which of the available biomarkers of oxidative stress are most specific, sensitive and selective.

The carbon tetrachloride model was the initial model since its mechanism of toxicity is well studied and documented. The group provided the samples to all investigators and performed several measurements. The results show that there are at least two markers of oxidative stress plasma levels of malondialdehyde and isoprostanes. Further goals of this study are to evaluate the most reliable markers of different oxidative insults in rodent models, non-human primates and, finally, in human populations.

The group has pioneered the application of the electron spin resonance spin-trapping technique to biochemical, pharmacological and toxicological problems with particular emphasis on the use of spin traps in vivo. The in vivo experiments are critical because, unless free radical Metabolism can be demonstrated with a whole animal model, there will always be some question as to their actual existence in biology. With the aid of the ESR technique, the group has demonstrated the formation of free radicals from rancid unsaturated fatty acids, established the role of hydroxyl radicals in iron and copper toxicity and implicated the involvement of an ethanol-derived free radical in alcohol-induced cirrhosis of the liver. Although the Free Radical Metabolism Group in these and many other investigations has played a leading role in the in vivo detection of free radicals, these investigations have been limited to rodents. Group members are attempting to extend these studies to humans. The recent detection of nitric oxide from hydroxyurea as HbNO in sickle cell anemia and adult leukemia patients has been accomplished for the first time.