Bilirubin and glutathione have complementary antioxidant and cytoprotective roles

Thomas W. Sedlak, Masoumeh Saleh, Daniel S. Higginson, Bindu D. Paul, Krishna R. Juluri, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

292 Scopus citations


Glutathione (GSH) and bilirubin are prominent endogenous antioxidant cytoprotectants. Despite tissue levels that are thousands of times lower than GSH, bilirubin is effective because of the biosynthetic cycle wherein it is generated from biliverdin by biliverdin reductase (BVR). When bilirubin acts as an antioxidant, it is oxidized to biliverdin, which is immediately reduced by BVR to bilirubin. Why does the body employ both of these 2 distinct antioxidant systems? We show that the water-soluble GSH primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation. Mice with deletionofheme oxygenase-2, which generates biliverdin, display greater lipid than protein oxidation, while the reverse holds for GSH depletion. RNA interference depletion of BVR increases oxidation of lipids more than protein. Depletion of BVR or GSH augments cell death in an oxidant-specific fashion.

Original languageEnglish (US)
Pages (from-to)5171-5176
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Mar 31 2009

ASJC Scopus subject areas

  • General


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