Redox state, oxidative stress, and molecular mechanisms of protective and toxic effects of bilirubin on cells.

Unconjugated bilirubin (UCB) is the major degradation product of the heme catabolism. UCB is a potent antioxidant molecule as well as an indirect pro-oxidant generator. Growing evidence suggests that its major cellular effects are mediated by inhibiting proliferation in cancer cell lines and eliciting cytotoxicity, particularly in neurons and glial cells. Here we describe studies showing that alteration of the redox status and generation of oxidative stress are likely early events responsible for UCB-induced cytotoxicity. We then elucidate some of the molecular pathways that govern these effects.