Bilirubin: Both villain and hero?

Bilirubin, the bile pigment that yellows the skin of babies born with jaundice, is generally considered a toxic molecule. According to a new study, however, bilirubin may actually protect cells from dangerous oxygen-containing molecules called free radicals.

Bilirubin forms during the breakdown of hemoglobin, the oxygen-carrying protein in blood cells, and can build up to high concentrations in the blood. Several lines of evidence indicate that bilirubin is toxic, but why then is there a specific enzyme that converts the seemingly harmless molecule known as bilverdin into bilirubin?

Scientists puzzled by this question have unearthed data suggesting that bilirubin, when present at the right concentration, is helpful instead of harmful. A research team headed by Solomon H. Snyder of Johns Hopkins University School of Medicine in Baltimore reports that bilirubin protects brain cells growing in lab dishes from the damage typically caused by hydrogen peroxide, a free radical.

The scientists compared normal cells with ones in which the bilirubin-making enzyme was inhibited. The normal cells were able to survive a dose of hydrogen peroxide 10,000 times greater than the lethal dose for the bilirubin-deprived cells. The investigators report their findings in the Dec. 10 Proceedings of the National Academy of Sciences.

Snyder and his colleagues also garnered evidence for a mechanism by which bilirubin, which is altered when it defuses free radicals, is recycled back into its original form. This reuse amplifies its protective powers. A protective role for bilirubin may explain previous findings that have linked low blood concentrations of the molecule to cancer, heart attacks, and other diseases, the scientists note.

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