Tracking Free Radicals To The Site Of Action

December 09, 1997

The power of an innovative method to directly measure the damaging activity of free radicals in the body was further confirmed in a recent study from the laboratory of Garret A. FitzGerald, MD, chairman of pharmacology. The technique, developed by FitzGerald and his colleagues and first reported last year, assesses urinary levels of a stable end product -- an isoprostane -- that results from free-radical attack on certain fatty molecules in tissues throughout the body. Previous experiments by the Penn team had shown that levels of this isoprostane are elevated in cigarette smokers and that antioxidant vitamins C and E together or vitamin C alone lower these levels. Those findings strongly suggested that free-radical tissue injury may contribute to the cardiovascular damage and disease associated with smoking and that targeted pharmaceutical interventions with proven antioxidant drugs might be useful, perhaps even prior to overt disease symptoms.

Now, as reported in the October 15 issue of the Journal of Clinical Investigation, the researchers used the new test to find high levels of the isoprostane in atherosclerotic plaque tissue removed from blocked neck arteries during a surgical procedure called an endarterectomy. They also used an antibody to the isoprostane to locate even more specifically its occurrence in the diseased tissue, showing its presence in two types of cells known to be major players in the development of atherosclerotic lesions. "Here we have a marker of the actual events at the site of the action," FitzGerald notes. "It's a real handle on the oxidant process in atherogenesis. And it means that we can now devise clinical studies to test the efficacy of drugs to limit free-radical damage." In the study, FitzGerald and his coworkers also reported isolation of a second biochemical tag for free-radical damage, providing an important additional tool for accurate analysis of a process increasingly implicated in a wide array of age-associated diseases.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation. In federal fiscal year 1996, the medical center received $149 million. In addition, for the second consecutive year, the institution posted the highest growth rate in research activity -- 9.1 percent -- of the top-ten U.S. academic medical centers during the same period. News releases from the medical center are available to reporters by direct E-mail, fax, or U.S. mail, upon request. They are also posted to the center's webpage (http://www.med.upenn.edu) and EurekAlert! (http://www.eurekalert.org), a resource sponsored by the American Association for the Advancement of Science.

University of Pennsylvania School of Medicine

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