Bilirubin, an old tetrapyrrolic compound that had occurred on Earth early on, is the final product of the catabolic heme pathway in the intravascular bed. Data from recent decades revealed its enormous bioactivity in a human body, including antioxidant, anti-inflammatory, immunosuppressive, antiproliferative, and even cell signaling activities that translate into beneficial effects of mildly elevated serum bilirubin concentrations resulting in prevention or amelioration of progression of many diseases of civilization. Furthermore, recent advances in bilirubin research have changed our understanding of bilirubin metabolism in the neonatal period, with discoveries of bilirubin reductase of bacterial origin in the intestinal lumen with direct pathophysiological and clinical implications. Similarly, our knowledge of the pathophysiology of neonatal jaundice phototherapy has improved substantially, although we are still at the beginning of the path to understand all the pathophysiological aspects and reveal related clinical implications. BULLET POINTS: Recent advances in our understanding of bilirubin metabolism with clear clinical implications, as well as other, so far putative, translational impacts. Demonstration of the beneficial biological potential of bilirubin, its evolutionary and ontogenetic functions, its possible role in chronobiology, and its correlation with increased fitness in elite athletes (a sort of gain of function). Discussion on the protective role of physiological neonatal jaundice. Inspiration for further basic and clinical research in specific fields of bilirubin metabolism.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Although bilirubin is a proven antioxidant substance and a protective factor against the development of various diseases, in emergency medicine, its increased concentration is considered solely a marker of organ damage and negative prognosis. However, clinical data on the role of bilirubin in cardiac arrest (CA) and reperfusion injury, are sparse. The presented study investigates the protective effects of increased serum bilirubin concentrations and genetic determinants (UGT1A1 promoter variations) on the outcomes of patients with refractory out-of-hospital CA (r-OHCA) in a randomized population. METHODS: Between March 1, 2013, and October 25, 2020, 256 randomized Prague OHCA patients with r-OHCA were evaluated for inclusion and categorized as having increased (>10 µmol/l) or low/normal serum bilirubin concentrations on hospital arrival and present or absent genetic variations for mild hyperbilirubinemia. The primary outcome was survival with a good neurological outcome (defined as cerebral performance category 1-2) 180 days after randomization. RESULTS: Finally, 164 patients were included in the bilirubin concentration analysis. Favorable neurological survival after 180 days occurred in 50 of 99 patients (50.5 %) in the group with higher initial serum bilirubin concentrations and 18 of 65 patients (27.7 %) in the low-bilirubin group (absolute difference 22.8 [8.1-37.5]; P = 0.006). The effect persisted also in multivariable analysis (OR for favorable outcome = 3.02 [95 % CI = 1.16-7.84]; P = 0.023). Genetic predisposition for mild hyperbilirubinemia was not associated with any patient outcomes. CONCLUSIONS: A higher initial serum bilirubin concentration predicts better outcomes in patients with refractory OHCA regardless of the treatment used. UGT1A1 gene promotor variations are not associated with refractory OHCA patient outcomes.

• Klíčová slova
• Antioxidants, Bilirubin, Cardiac arrest, Genetic variations, Mechanical circulatory support, Oxidative stress,
• Publikační typ
• časopisecké články MeSH

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

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.

• Klíčová slova
• Alzheimer’s disease, MAFLD, NRF2, Parkinson’s disease, bilirubin, cancer, heme-oxygenase, herbal medicine, neurodegeneration, nutraceuticals,
• MeSH
• bilirubin MeSH
• biliverdin MeSH
• dospělí MeSH
• hem MeSH
• hemová oxygenasa (decyklizující) MeSH
• játra MeSH
• lidé MeSH
• nemoci mozku * MeSH
• podpora zdraví * MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bilirubin MeSH
• biliverdin MeSH
• hem MeSH
• hemová oxygenasa (decyklizující) MeSH