Abstract
Background: Severe hyperbilirubinemia can cause permanent neurological damage in particular in neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated bilirubin concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects.
Methods: Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) and neuronal (SH-SY5Y) cell lines were exposed to increasing concentration of bilirubin. iUCB, cytotoxicity, intracellular reactive oxygen species (ROS) concentrations, and antioxidant capacity (50% efficacy concentration (EC50)) were determined. Results: Exposure of SH-SY5Y to UCB concentration > 3.6 mu M (iUCB of 25 ng/mg) and >15 mu M in H5V and HK2 cells (iUCB of 40 ng/mg) increased intracellular ROS production (p 25 ng/mg protein resulted in a prooxidant and cytotoxic effects.
UCB metabolism was found to be cell-specific resulting in different iUCB.