Biliverdin as a disease-modifying agent: An integrated viewpoint

• Published in: Free Radical Biology and Medicine
• Main Author: Mancuso, Cesare
• Format: Article in Journal/Newspaper
• Language: English
• Published: ELSEVIER SCIENCE INC 2023
• Subjects: Bilirubin; Carbon monoxide; Drug development; Green jaundice; Heme oxygenase; Translational research; Settore BIO/14 - FARMACOLOGIA; inuit
• Online Access: https://hdl.handle.net/10807/259298; https://doi.org/10.1016/j.freeradbiomed.2023.07.015

Biliverdin is one of the three by-products of heme oxygenase (HO) activity, the others being ferrous iron and carbon monoxide. Under physiological conditions, once formed in the cell, BV is reduced to bilirubin (BR) by the biliverdin reductase (BVR). However, if BVR is inhibited by either genetic variants, as occurs in the Inuit ethnicity, or dioxin intoxication, BV accumulates in cells giving rise to a clinical syndrome known as green jaundice. Preclinical studies have demonstrated that BV not only has a direct antioxidant effect by scavenging free radicals, but also targets many signal transduction pathways, such as BVR, soluble guanylyl cyclase, and the aryl hydrocarbon receptor. Through these direct and indirect mechanisms, BV has shown beneficial roles in ischemia/reperfusion-related diseases, inflammatory diseases, graft-versus-host disease, viral infections and cancer. Unfortunately, no clinical data are available to confirm these potential therapeutic effects and the kinetics of exogenous BV in humans is unknown. These limitations have so far excluded the possibility of transforming BV from a mere by-product of heme degradation into a disease-modifying agent. A closer collaboration between basic and clinical researchers would be advantageous to overcome these issues and promote translational research on BV in free radical-induced diseases.