Biliverdin reductase: A major physiologic cytoprotectant

David E. Barañano, Mahil Rao, Christopher D. Ferris, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

830 Scopus citations


Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverdin reductase of biliverdin, a product of heme oxygenase activity. Bilirubin is a potent antioxidant that we show can protect cells from a 10,000-fold excess of H2O2. We report that bilirubin is a major physiologic antioxidant cytoprotectant. Thus, cellular depletion of bilirubin by RNA interference markedly augments tissue levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic antioxidant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxidant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin.

Original languageEnglish (US)
Pages (from-to)16093-16098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Dec 10 2002

ASJC Scopus subject areas

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