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Transplantation Reviews (Orlando, Fla.) Oct 2018In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival... (Review)
Review
In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.
Topics: Antioxidants; Bilirubin; Graft Rejection; Humans; Kidney Transplantation
PubMed: 29983261
DOI: 10.1016/j.trre.2018.06.003 -
Seminars in Perinatology Jun 2011Neonatal jaundice (hyperbilirubinemia), which is extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in... (Review)
Review
Neonatal jaundice (hyperbilirubinemia), which is extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or "free") bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates, including premature infants, no widely available method exists to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need.
Topics: Bilirubin; Fluorometry; Humans; Infant, Newborn; Jaundice, Neonatal; Serum Albumin; Serum Albumin, Human; Spectrophotometry
PubMed: 21641486
DOI: 10.1053/j.semperi.2011.02.007 -
Current Hypertension Reports Oct 2019To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases. (Review)
Review
PURPOSE OF REVIEW
To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases.
RECENT FINDINGS
Several investigations from human patient populations and experimental animal models have shown that bilirubin improves cardiorenal and metabolic dysfunction. The latest studies found an entirely new function of bilirubin suggesting that it acts as a hormone signaling molecule capable of activating nuclear receptors for burning fat, which may explain several of its protective actions. This review highlights the current findings (within the last 3 years) regarding cardiorenal and metabolic protective effects of bilirubin and the latest mechanism(s) that may be mediating these effects.
Topics: Animals; Antioxidants; Bilirubin; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Metabolic Diseases
PubMed: 31599366
DOI: 10.1007/s11906-019-0994-z -
Immunity, Inflammation and Disease Dec 2023Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels... (Meta-Analysis)
Meta-Analysis
AIMS
Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE.
METHODS
The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails.
RESULTS
Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06).
CONCLUSION
The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.
Topics: Humans; Bilirubin; Case-Control Studies; China; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 38156396
DOI: 10.1002/iid3.1115 -
International Journal of Molecular... Jun 2022Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is... (Review)
Review
Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is an inducible form of HO that is upregulated by oxidative stress, nitric oxide, CO, and hypoxia, whereas HO-2 is a constitutive form that regulates vascular tone and homeostasis. In brains injured by trauma, ischemia-reperfusion, or Alzheimer's disease (AD), the long-term expression of HO-1 can be detected, which can lead to cytotoxic ferroptosis via iron accumulation. In contrast, the transient induction of HO-1 in the peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, and mitochondrial biogenesis) and neurovascular protective effects through the CO-mediated signaling pathway, the antioxidant properties of bilirubin, and the iron-mediated ferritin synthesis. In this review, we discuss the dual roles of HO-1 and its metabolites in various neurovascular diseases, including age-related macular degeneration, ischemia-reperfusion injury, traumatic brain injury, Gilbert's syndrome, and AD.
Topics: Bilirubin; Biliverdine; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Iron
PubMed: 35806040
DOI: 10.3390/ijms23137041 -
BMC Medicine Sep 2020Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian...
BACKGROUND
Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.
METHODS
In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.
RESULTS
The associations between circulating UCB levels and CRC risk differed by sex (P = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P ≥ 0.2).
CONCLUSIONS
Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
Topics: Adult; Aged; Bilirubin; Case-Control Studies; Colorectal Neoplasms; Europe; Female; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors
PubMed: 32878631
DOI: 10.1186/s12916-020-01703-w -
Journal of Biomedical Optics Oct 2023Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and...
SIGNIFICANCE
Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and assessment of clinical and physiological vascular functions. Clinically, it is useful to assess multiple different chromophores with a single technique or instrument.
AIM
To investigate the possibility of estimating the concentration of four chromophores, bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin from diffuse reflectance spectra in the visible region.
APPROACH
A new diffuse reflectance spectroscopic method based on the multiple regression analysis aided by Monte Carlo simulations for light transport was developed to quantify bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin. Three different experimental animal models were used to induce hyperbilirubinemia, hypoxemia, and melanogenesis in rats.
RESULTS
The estimated bilirubin concentration increased after ligation of the bile duct and reached around at 50 h after the onset of ligation, which corresponds to the reference value of bilirubin measured by a commercially available transcutaneous bilirubin meter. The concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin decreased and increased, respectively, as the fraction of inspired oxygen decreased. Consequently, the tissue oxygen saturation dramatically decreased. The time course of melanin concentration after depilation of skin on the back of rats was indicative of the supply of melanosomes produced by melanocytes of hair follicles to the growing hair shaft.
CONCLUSIONS
The results of our study showed that the proposed method is capable of the evaluation of percutaneous bilirubin level, skin hemodynamics, and melanogenesis in rats, and that it has potential as a tool for the diagnosis and management of hyperbilirubinemia, hypoxemia, and pigmented skin lesions.
Topics: Rats; Animals; Melanins; Bilirubin; Spectrum Analysis; Skin; Hypoxia; Hemoglobins; Oxyhemoglobins; Hyperbilirubinemia
PubMed: 37915398
DOI: 10.1117/1.JBO.28.10.107001 -
Archives of Disease in Childhood Nov 1975
Topics: Bilirubin; Blood Specimen Collection; History, 20th Century; Humans; Infant, Newborn; Jaundice, Neonatal; Phototherapy; Sunlight
PubMed: 1108807
DOI: 10.1136/adc.50.11.833 -
JPEN. Journal of Parenteral and Enteral... 2010The author has previously shown that intravenous lipid intake may be associated with an increase in unbound bilirubin in infants < or =28 weeks gestational age. The...
BACKGROUND
The author has previously shown that intravenous lipid intake may be associated with an increase in unbound bilirubin in infants < or =28 weeks gestational age. The objective of this study was to evaluate whether this increase in unbound bilirubin is mediated by free fatty acids and to examine the secondary effect of free fatty acids on bilirubin-albumin binding affinity.
METHODS
A prospective study was conducted to include 26 infants < or =32 weeks gestational age with indirect hyperbilirubinemia and receiving intravenous lipids during the first 10 postnatal days. Blood samples were collected for unbound bilirubin, binding affinity, and free fatty acid measurement at varying intravenous lipid intakes (1-3 g/kg/d). Regression analyses were performed to evaluate the roles of free fatty acids and binding affinity as mediators.
RESULTS
Intravenous lipid intake was significantly associated with an increase in free fatty acids and unbound bilirubin in infants < or =28 weeks but not >28 weeks gestational age. In infants < or =28 weeks gestational age, each unit increase in free fatty acids was significantly associated with a decrease in binding affinity, which was significantly associated with an increase in unbound bilirubin.
CONCLUSIONS
In infants < or =28 weeks gestational age, intravenous lipid intake may be associated with an increase in unbound bilirubin, and this is mediated by an increase in free fatty acids and a secondary decrease in binding affinity. In infants >28 weeks gestational age, higher intravenous lipid intake may be used because it is unassociated with increases in free fatty acids and unbound bilirubin.
Topics: Albumins; Bilirubin; Dietary Fats; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Humans; Hyperbilirubinemia; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Prospective Studies; Protein Binding; Regression Analysis
PubMed: 20631387
DOI: 10.1177/0148607110362529 -
Stem Cell Reports Nov 2023UGT1A1 (UDP glucuronosyltransferase family 1 member A1) is the primary enzyme required for bilirubin conjugation, which is essential for preventing hyperbilirubinemia....
UGT1A1 (UDP glucuronosyltransferase family 1 member A1) is the primary enzyme required for bilirubin conjugation, which is essential for preventing hyperbilirubinemia. Animal models lack key human organic anion transporting polypeptides with distinct epigenetic control over bilirubin metabolism, necessitating a human model to interrogate the regulatory mechanism behind UGT1A1 function. Here, we use induced pluripotent stem cells to develop human liver organoids that can emulate conjugation failure phenotype. Bilirubin conjugation assays, chromatin immunoprecipitation, and transcriptome analysis elucidated the role of glucocorticoid antagonism in UGT1A1 activation. This antagonism prevents the binding of transcriptional repressor MECP2 at the expense of NRF2 with associated off-target effects. Therefore, we introduced functional GULO (L-gulonolactone oxidase) in human organoids to augment intracellular ascorbate for NRF2 reactivation. This engineered organoid conjugated more bilirubin and protected against hyperbilirubinemia when transplanted in immunosuppressed Crigler-Najjar syndrome rat model. Collectively, we demonstrate that our organoid system serves as a manipulatable model for interrogating hyperbilirubinemia and potential therapeutic development.
Topics: Humans; Animals; Rats; Bilirubin; NF-E2-Related Factor 2; Liver; Crigler-Najjar Syndrome; Hyperbilirubinemia; Glucuronosyltransferase; Pluripotent Stem Cells
PubMed: 37832542
DOI: 10.1016/j.stemcr.2023.09.006