Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Università Cattolica Del Sacro Cuore, Largo F. Vito, 1, 00168, Rome, Italy.
Free Radic Biol Med. 2023 Oct;207:133-143. doi: 10.1016/j.freeradbiomed.2023.07.015. Epub 2023 Jul 15.
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.
胆红素是血红素加氧酶 (HO) 活性的三种副产物之一，其他两种是亚铁离子和一氧化碳。在生理条件下，BV 一旦在细胞中形成，就会被胆红素还原酶 (BVR) 还原为胆红素 (BR)。然而，如果 BVR 被遗传变异（如因纽特人）或二恶英中毒抑制，BV 会在细胞中积累，导致一种称为绿色黄疸的临床综合征。临床前研究表明，BV 不仅通过清除自由基具有直接的抗氧化作用，而且还靶向许多信号转导途径，如 BVR、可溶性鸟苷酸环化酶和芳香烃受体。通过这些直接和间接的机制，BV 在与缺血/再灌注相关的疾病、炎症性疾病、移植物抗宿主病、病毒感染和癌症中显示出有益的作用。不幸的是，目前尚无临床数据证实这些潜在的治疗效果，并且人体中外源 BV 的动力学尚不清楚。这些限制迄今为止排除了将 BV 从血红素降解的副产品转变为疾病修饰剂的可能性。基础研究人员和临床研究人员之间更密切的合作将有利于克服这些问题，并促进自由基诱导疾病中 BV 的转化研究。
