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Trends in Molecular Medicine Apr 2023Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent... (Review)
Review
Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent immunosuppressive effects associated with long-term pathophysiological sequelae. It has been recently recognized as a hormone with endocrine actions and interconnected effects on various cellular signaling pathways. Current studies show that bilirubin also decreases adiposity and prevents metabolic and cardiovascular diseases. All in all, the physiological importance of bilirubin is only now coming to light, and strategies for increasing plasma bilirubin levels to combat chronic diseases are starting to be considered. This review discusses the beneficial effects of increasing plasma bilirubin, incorporates emerging areas of bilirubin biology, and provides key concepts to advance the field.
Topics: Humans; Bilirubin; Heme Oxygenase-1; Cardiovascular Diseases; Reactive Oxygen Species
PubMed: 36828710
DOI: 10.1016/j.molmed.2023.01.007 -
Journal of Hepatology Oct 2023Gilbert's syndrome, also known as benign hyperbilirubinaemia, was described more than 100 years ago. It has usually been considered a physiological abnormality... (Review)
Review
Gilbert's syndrome, also known as benign hyperbilirubinaemia, was described more than 100 years ago. It has usually been considered a physiological abnormality characterised by a mild elevation of the systemic level of unconjugated bilirubin, in the absence of any underlying liver or overt haemolytic disease. However, since the re-discovery of the potent antioxidant effects of bilirubin in the late 1980s, as well as multiple intracellular signalling pathways affected by bilirubin, an ever-increasing body of evidence suggests that individuals with Gilbert's syndrome may benefit from the mild hyperbilirubinaemia and are actually protected from the development of a wide variety of "diseases of civilisation" such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases. This review analyses the current state of medical knowledge given recent discoveries in this rapidly developing field, as well as their possible clinical significance, and provides a new perspective on this condition.
Topics: Humans; Gilbert Disease; Hyperbilirubinemia; Liver; Bilirubin; Antioxidants
PubMed: 37390966
DOI: 10.1016/j.jhep.2023.06.004 -
Trends in Endocrinology and Metabolism:... Mar 2018Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin... (Review)
Review
Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood. In this review, we discuss the relationship of hepatic bilirubin signaling to the intestinal microbiota and its regulation of the liver-gut axis, as well as its capacity to mediate these processes.
Topics: Animals; Bilirubin; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Liver; Signal Transduction
PubMed: 29409713
DOI: 10.1016/j.tem.2018.01.002 -
Pediatric Research Mar 2016Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be... (Review)
Review
Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.
Topics: Animals; Bile; Bilirubin; Crigler-Najjar Syndrome; Gilbert Disease; Glucuronic Acid; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Hereditary; Hyperbilirubinemia, Neonatal; Jaundice, Chronic Idiopathic; Liver
PubMed: 26595536
DOI: 10.1038/pr.2015.247 -
American Journal of Physiology.... Feb 2021Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene... (Review)
Review
Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for patients with hypobilirubinemia, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.
Topics: Animals; Bilirubin; Energy Metabolism; Gene Expression Regulation; Gilbert Disease; Heme; Hormones; Humans; Hyperbilirubinemia; Metabolic Networks and Pathways; PPAR alpha
PubMed: 33284088
DOI: 10.1152/ajpendo.00405.2020 -
Journal of Hepatology Dec 2021Bilirubin is a tetrapyrrolic compound originating from heme catabolism. Although originally considered only a potentially dangerous waste product, it has become...
Bilirubin is a tetrapyrrolic compound originating from heme catabolism. Although originally considered only a potentially dangerous waste product, it has become increasingly evident that this molecule represents an important modulator of various biological functions in the human body. Bilirubin appears to have versatile functions, from cell signaling (behaving almost like a "real" hormonal substance), modulation of metabolism, to immune regulation, affecting biological activities with apparent clinical and even therapeutic consequences. These activities may be the reason for the lower incidence of diseases of civilisation (cardiovascular diseases, arterial hypertension, diabetes, obesity, metabolic syndrome, certain cancers, autoimmune, and neurodegenerative diseases) observed in individuals with a chronic mild unconjugated hyperbilirubinemia, a typical sign of Gilbert's syndrome. While higher serum concentrations of unconjugated bilirubin may serve as an important protective factor against these diseases, low levels of bilirubin are associated with the opposite effect.
Topics: Bilirubin; Color; Heme; Humans; Hyperbilirubinemia
PubMed: 34153399
DOI: 10.1016/j.jhep.2021.06.010 -
Current Opinion in Gastroenterology May 2017Jaundice, the physical finding associated with hyperbilirubinemia, results when the liver is unable to properly metabolize or excrete bilirubin. The purpose of this... (Review)
Review
PURPOSE OF REVIEW
Jaundice, the physical finding associated with hyperbilirubinemia, results when the liver is unable to properly metabolize or excrete bilirubin. The purpose of this review is to examine some of the most common causes of jaundice in adults, provide insight into the diagnostic evaluation of jaundice, and review information on the outcomes of patients with jaundice.
RECENT FINDINGS
An elevated level of bilirubin almost always indicates the presence of an underlying disease state. The best approach to evaluating a patient with jaundice is to start with a careful history and physical examination, followed by imaging assessment of the biliary tree and liver. There are algorithm models that incorporate bilirubin levels in their predictor models for outcomes in patients with chronic liver disease (i.e., the model for end-stage liver disease). However, there are few studies that have examined the outcomes of patients with jaundice.
SUMMARY
Evaluation of patients with jaundice starts with a careful history and physical examination, followed by directed imaging of the biliary tree and liver. Although jaundice is generally believed to be a serious medical condition, there is little literature that addresses outcomes in patients with jaundice.
Topics: Bilirubin; Diagnosis, Differential; Hepatitis, Viral, Human; Hepatocytes; Humans; Hyperbilirubinemia; Liver Diseases; Prognosis
PubMed: 28333690
DOI: 10.1097/MOG.0000000000000354 -
Physiological Reviews Jul 2020Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated... (Review)
Review
Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.
Topics: Bilirubin; Brain; Humans; Infant, Newborn; Intestinal Mucosa; Liver
PubMed: 32401177
DOI: 10.1152/physrev.00004.2019 -
Hong Kong Medical Journal = Xianggang... Jun 2018Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some... (Review)
Review
Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some self-limiting and others potentially life-threatening. This article aims to provide a concise review of the common medical and surgical causes in children and discuss their diagnosis and management.
Topics: Bilirubin; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Jaundice; Laparoscopy
PubMed: 29807950
DOI: 10.12809/hkmj187245 -
Anales de Pediatria Feb 2020Neonatal jaundice is common, especially in premature infants. Compliance with treatment protocols and standard serum bilirubin curves forces the clinician to separate... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Neonatal jaundice is common, especially in premature infants. Compliance with treatment protocols and standard serum bilirubin curves forces the clinician to separate the child from the mother after birth for short phototherapy. The objective of this study is to evaluate the effectiveness and safety of two innovative devices for phototherapy including a LED light mesh: one sleeping bag and one blanket compared to conventional hospital or ambulatory phototherapy.
METHODS
Two randomised clinical trials were conducted: one with newborns >2,000g at birth in the Neonatal Care Unit and the other with premature infants followed-up in an outpatient clinic (PMC). The gold standard for bilirubin measurement was serum bilirubin, and ambulatory controls were performed with the Bilicheck®. Parents and health personnel completed a questionnaire on comfort and perceptions.
RESULTS
In the study using the bag, a linear regression was performed for the decrease in bilirubin in mg/dL/h, controlling by early jaundice (<36h) and the device type. The results were similar between the 2 devices. For the blanket trial in the PMC, the decrease in bilirubin levels with the new device was significantly greater with no differences in temperatures, duration of phototherapy, re-admission, mortality, or side effects for both trials. Parents and staff satisfaction with the two devices was identical for the 2 trials.
CONCLUSION
These 2 small studies add a 'grain of sand' to humanisation of newborn care, avoiding the mother-and-child separation for both the intra-hospital high-risk hyperbilirubinaemia, as well as for the lower-risk hyperbilirubinaemia in an outpatient clinic.
Topics: Bilirubin; Female; Humans; Infant, Newborn; Infant, Premature; Jaundice, Neonatal; Male; Phototherapy; Surveys and Questionnaires
PubMed: 30979682
DOI: 10.1016/j.anpedi.2019.02.008