Tracking Dangerous Radicals

Like a notorious suspect able to stay one step ahead of the law, corrosive oxygen compounds called free radicals are implicated in many diseases but leave little hard evidence of their handiwork. Now there may be a better tool for nailing these chemical culprits: a simple urine test that can track an indicator of free-radical damage following bypass surgery or heart attack therapy. The test, described in tomorrow's issue of the journal Circulation, might be used to devise better antioxidant vitamin therapies against free radicals and to explore the mechanism of these compounds in cancer and other diseases.

After bypass surgery and other cardiac therapies, increased blood flow to the oxygen-deprived heart often oxidizes and damages heart tissue. Such patients, scientists have found, have elevated blood levels of oxidized compounds. But blood tests are a poor indicator of free-radical damage, as the mechanical process of drawing blood itself can oxidize chemicals.

To try to get a better handle on free-radical damage, Garret FitzGerald and his colleagues at the University of Pennsylvania Medical Center in Philadelphia developed a test for urine levels of 8-epi PGF-2-alpha, a chemical formed after free radicals such as peroxide and superoxide attack the common lipid arachidonic acid. FitzGerald's group tested for the byproduct in two groups of patients with increased heart blood flow: heart attack patients treated with a clot-busting drug, and people whose arteries had been clamped off during bypass surgery, then reopened. In 12 heart attack patients, levels of 8-epi PGF-2-alpha were on average two and a half times higher than normal. And in five bypass patients, levels of the chemical rose during the operation, peaked 15 minutes after clamp removal, and returned to normal within 24 hours.

Experts are impressed with the urine test. "There are other methods, but they have always been suspect. This is more elegant," says Steven Prescott, who studies free-radical metabolism at the University of Utah. FitzGerald predicts that the test will help to determine the best dosage of antioxidants that could prevent free-radical damage in cardiac patients. "We still don't know what is an antioxidant dose of vitamins. This marker gives us a quantitative handle on the process," he says. Once his group has refined the test, FitzGerald says, they'll try to measure free-radical damage in Alzheimer's and other diseases.

Posted in Biology, Health