Bilirubin as savior of biological system

Bilirubin is more than just the final product of heme catabolism. Today it is considered to be a fundamental substance which acts as an antioxidant and anti-inflammatory agent in the serum. It can neutralize free radicals and prevent peroxidation of lipids. In addition there is evidence that it protects the cardiovascular system, neuronal systems, the hepatobiliary system, the pulmonary system and the immune system. Recently the use of pharmacological agents which augment expression of Heme oxigenase 1 (HO-1) has been investigated. Consequently its metabolites such as carbon monoxide (CO), biliverdin (BV) and bilirubin (BR) could become parts of a therapeutic strategy for treatment of various inflammatory illnesses. Reactive oxygen species (ROS) and signaling events are involved in the pathogenesis of endothelial dysfunction and represent a major contribution to vascular regulation. But depending on the amount of ROS production it might have toxic or protective effects. Despite a large number of negative outcomes in large clinical trials (e.g., HOPE, HOPE-TOO), antioxidant molecules and agents are important players to influence the critical balance between production and elimination of reactive oxygen and nitrogen species. With the present review we would like to highlight the important antioxidant role of the HO system and especially discuss the contribution of the biliverdin, bilirubin, and biliverdin reductase (BVR) to these beneficial effects.