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Infant Jaundice Sign Has Its Plus Side

Bilirubin is a blue-ribbon antioxidant

MONDAY, Nov. 25, 2002 (HealthDayNews) -- New parents know bilirubin as the yellow signal of infant jaundice, so they might be surprised to hear that the blood by-product also plays an important beneficial role.

Scientists have found that bilirubin, pigment that is released in the breakdown of red cells, is among the body's most powerful antioxidants and can shield tissues from highly reactive oxygen cells called free radicals. Cells deprived of the substance are overwhelmed by harmful oxygen molecules and commit suicide.

"Bilirubin in all of the cells in our body is probably the most important means of protecting cells from oxidative damage," said Dr. Solomon Snyder, director of the department of neuroscience at Johns Hopkins School of Medicine in Baltimore and a co-author of the study.

The findings, reported this week in the Proceedings of the National Academy of Sciences, could help explain why adults with elevated bilirubin appear less prone to heart disease and deadly heart attacks.

Studies have also shown that as blood concentrations of bilirubin rise, the risk of some cancers falls, and premature babies with increased bilirubin are less vulnerable to eye damage from oxygen in their respirators.

Bilirubin generates a chemical called biliverdin, which would otherwise dissolve in water and pass out of the urine, as it does in birds. But in humans, the enzyme biliverdin reductase converts biliverdin back into the pigment. The body must make a second enzyme to turn bilirubin into a water-soluble molecule.

This energy-intensive cycle has led some researchers to ask whether bilirubin might have a desirable function that evolution has sought to preserve.

"It seems stupid" of nature to be so convoluted, Snyder said. "But the answer is, it's very brilliant."

Bilirubin usually is present in low levels in cells; in high amounts it can be toxic and even deadly. But the cycle makes each molecule of the pigment a sponge, capable of neutralizing 10,000 oxygen radicals. That's 10,000 times more efficient than glutahione, the cellular substance scientists previously considered the body's main oxygen absorber, Snyder said.

In previous work, Snyder and his colleagues showed that bilirubin can save brain cells from oxidation. In the new study, they prevented human cancer and rat brain cells from making biliverdin reductase. The change made the cells much more vulnerable to oxidation by hydrogen peroxide than tissue with the functioning enzyme.

Snyder said stroke patients may be one group to benefit from the discovery. Mouse studies have shown that rodents missing bilirubin suffer much greater damage after strokes than those with the molecule.

"If you could deliver bilirubin in relatively small concentrations so it had access to the recycling machinery, it would be a very good anti-stroke drug," he said. Hopkins researchers are now embarking on studies of that approach, he added.

Some other experts may view the new research with an, er, jaundiced eye.

Dr. Paul Berk, a liver specialist at Mount Sinai School of Medicine in New York City, said, "The story about bilirubin's antioxidant properties goes back years, but it has never made it into the mainstream" of medicine.

"I would guess that most people think that this is a laboratory phenomenon," Berk added.

Still, Berk said that doesn't mean most people are right, and he admonished scientists to "keep an open mind" about bilirubin.

What To Do

To learn more about bilirubin, try the Children's Liver Disease Foundation from the U.K. For information on antioxidants, check out MEDLINEplus.

SOURCES: Solomon H. Snyder, M.D., director, department of neuroscience, Johns Hopkins University School of Medicine, Baltimore; Paul Berk, M.D., professor of medicine, Mount Sinai School of Medicine, New York; Nov. 25, 2002 Proceedings of the National Academy of Sciences
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