Bilirubin is the principal product of heme catabolism. High concentrations of the pigment are neurotoxic, yet slightly elevated levels are beneficial. Being a potent antioxidant, oxidative transformations of bilirubin occur in vivo and lead to various oxidized fragments. The mechanisms of their formation, intrinsic biological activities, and potential roles in human pathophysiology are poorly understood. Degradation methods have been used to obtain samples of bilirubin oxidation products for research. Here, we report a complementary, fully synthetic method of preparation. Our strategy leverages repeating substitution patterns in the parent tetracyclic pigment. Functionalized ready-to-couple γ-lactone, γ-lactam, and pyrrole monocyclic building blocks were designed and efficiently synthesized. Subsequent modular combinations, supported by metal-catalyzed borylation and cross-coupling chemistries, translated into the concise assembly of the structurally diverse bilirubin oxidation products (BOXes, propentdyopents, and biopyrrins). The discovery of a new photoisomer of biopyrrin A named lumipyrrin is reported. Synthetic bilirubin oxidation products made available in sufficient purity and quantity will support future in vitro and in vivo investigations.

• MeSH
• bilirubin * metabolismus   MeSH
• lidé MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• pyrroly * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bilirubin * MeSH
• pyrroly * MeSH

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.

• MeSH
• bilirubin krev   MeSH
• biologické markery krev   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká hyperbilirubinemie krev   diagnóza   terapie   MeSH
• novorozenecká žloutenka krev   diagnóza   terapie   MeSH
• novorozenecký screening * MeSH
• point of care testing * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• bilirubin MeSH
• biologické markery MeSH

Bilirubin is a yellow endogenous derivate of the heme catabolism. Since the 1980s, it has been recognized as one of the most potent antioxidants in nature, able to counteract 10,000× higher intracellular concentrations of H2O2. In the recent years, not only bilirubin, but also its precursor biliverdin, and the enzymes involved in their productions (namely heme oxygenase and biliverdin reductase; altogether the "yellow players"-YPs) have been recognized playing a protective role in diseases characterized by a chronic prooxidant status. Based on that, there is an ongoing effort in inducing their activity as a therapeutic option. Nevertheless, the understanding of their specific contributions to pathological conditions of the central nervous system (CNS) and their role in these diseases are limited. In this review, we will focus on the most recent evidence linking the role of the YPs specifically to neurodegenerative and neurological conditions. Both the protective, as well as potentially worsening effects of the YP's activity will be discussed.

• Klíčová slova
• bilirubin, bilirubin oxidation products, biliverdin, biliverdin reductase, central nervous system (CNS), heme, heme oxygenase, neurodegenerative diseases, yellow players,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH