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European Review For Medical and... May 2021The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in...
OBJECTIVE
The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus.
MATERIALS AND METHODS
A total of 60 Wistar albino rat puppies with experimental kernicterus model were included in the study. The Kernicterus was established administering a bilirubin injection via a cisterna magna puncture 30 minutes after ip drug injection. The puppies were divided into five groups with 12 in each group as shown below: a control group, bilirubin group, darbepoetin alpha group, topiramate group and darbepoetin alpha+ topiramate group. Darbepoetin alpha and/or topiramate were administered on day 5 intraperitoneally (ip). At the 6th and 24th hours, bilirubin induced neurological dysfunction (BIND) score was used to assess behavioral changes. Hearing functions were evaluated on days 10 and 28. On day 30, the Water Maze water tank test was implemented to evaluate spatial memory. The rats were sacrificed on days 6 and 34 and apoptosis in the globus pallidus and hippocampus was examined.
RESULTS
The BIND score was improved following darbepoetin alpha treatment. Neither darbepoetin alpha nor topiramate therapy ameliorate spatial memory. There were no significant differences between groups in terms of the auditory brainstem response (ABR). The combined use of darbepoetin alpha and topiramate lead to slight decrease in apoptosis.
CONCLUSIONS
Darbepoetin alpha or topiramate administration ameliorates bilirubin induced neurological dysfunction in experimental model of kernicterus.
Topics: Animals; Apoptosis; Bilirubin; Darbepoetin alfa; Female; Maze Learning; Morris Water Maze Test; Neurons; Rats; Rats, Wistar; Topiramate
PubMed: 34002833
DOI: 10.26355/eurrev_202105_25841 -
Molecular Pharmacology May 2017Hyperbilirubinemia, caused by the accumulation of unconjugated bilirubin, is one of the most common clinical diagnoses in both premature and term newborns. Owing to the... (Review)
Review
Hyperbilirubinemia, caused by the accumulation of unconjugated bilirubin, is one of the most common clinical diagnoses in both premature and term newborns. Owing to the fact that bilirubin is metabolized solely through glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, it is now known that immaturity of UGT1A1, in combination with the overproduction of bilirubin during the developmental stage, acts as a bottleneck to bilirubin elimination and predisposes the infant to high total serum bilirubin levels. Although neonatal jaundice is mostly benign, excessively high levels of serum bilirubin in a small percentage of newborns can cause bilirubin-induced neurologic dysfunction, potentially leading to permanent brain damage, a condition known as Although a large portion of hyperbilirubinemia cases in newborns are associated with hemolytic diseases, we emphasize here the impaired ability of UGT1A1 to eliminate bilirubin that contributes to hyperbilirubinemia-induced neurotoxicity in the developmental stage. As a series of hereditary UGT1A1 mutations have been identified that are associated with UGT1A1 deficiency, new evidence has verified that delayed expression of UGT1A1 during the early stages of neonatal development is a tightly controlled event involving coordinated intrahepatic and extrahepatic regulation. This review recapitulates the progress that has been made in recent years in understanding the causes and physiopathology of severe hyperbilirubinemia, investigating molecular mechanisms underlying bilirubin-induced encephalopathy, and searching for potential therapies for treating pathologic hyperbilirubinemia. Several animal models have been developed to make it possible to examine bilirubin-induced neurotoxicity from multiple directions. Moreover, environmental factors that may alleviate or worsen the condition of hyperbilirubinemia are discussed.
Topics: Animals; Bilirubin; Diet; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn
PubMed: 28283555
DOI: 10.1124/mol.116.107524 -
Archivos Argentinos de Pediatria Feb 2021Hyperbilirubinemia is the most common reason for consultation and hospitalization in the neonatal period. It requires a timely initiation of an effective treatment... (Review)
Review
Hyperbilirubinemia is the most common reason for consultation and hospitalization in the neonatal period. It requires a timely initiation of an effective treatment because newborn infants are especially vulnerable to damage caused by bilirubin in the central nervous system due to the characteristics typical of this stage of life. High bilirubin levels result in neurotoxicity and oxidative stress. However, molecular biology studies have demonstrated that bilirubin itself acts as a potent antioxidant. The objective of this update is to review the processes whereby bilirubin causes cell damage and determine its beneficial antioxidant effects. Knowing these mechanisms may facilitate a more accurate indication of a customized, effective, and timely phototherapy. Until new scientific advances are made, phototherapy should be prescribed based on expert consensus.
Topics: Antioxidants; Bilirubin; Humans; Hyperbilirubinemia; Oxidative Stress; Phototherapy
PubMed: 33458986
DOI: 10.5546/aap.2021.eng.e18 -
International Journal of Epidemiology Feb 2015Experimental studies suggest oxidative stress could lead to the development of hypertension. Serum bilirubin is a major contributor to the antioxidant capacity in blood...
BACKGROUND
Experimental studies suggest oxidative stress could lead to the development of hypertension. Serum bilirubin is a major contributor to the antioxidant capacity in blood plasma and has been identified as an independent cardiovascular risk factor in cohort studies. However, data on the relationship between bilirubin and blood pressure are scarce and inconclusive.
METHODS
We analysed data from the National Health and Nutrition Examination Surveys (NHANES) 1999-2012 (N=31069). Fifty multiple imputed data sets were generated and analysed to avoid selection/confounding bias due to excluding individuals/variables with missing values. A minimal sufficient adjustment set of variables (MSAS) needed to estimate the unconfounded effect of bilirubin on blood pressure and hypertension (systolic/diastolic blood pressure ≥ 140/90 mmHg or using antihypertensive medication) was identified using the back-door criterion and included in all regression models.
RESULTS
After adjustment for the MSAS variables, systolic blood pressure decreased progressively up to -2.5 mmHg (p<0.001) and the prevalence of hypertension was up to 25% lower (P<0.001) in those with bilirubin ≥ 1.0 mg/dl-the highest two deciles-compared with those with 0.1-0.4 mg/dl-the lowest decile. Sensitivity analyses showed these results were unlikely to be explained by residual confounding or selection bias.
CONCLUSIONS
High serum bilirubin may decrease the risk of hypertension by inactivating and inhibiting the synthesis of reactive oxygen species in vascular cells. Strategies to boost the bioavailability of circulating and tissue bilirubin or to mimic bilirubin's antioxidant properties could have a significant impact on prevention and control of hypertension as well as coronary heart disease.
Topics: Age Factors; Bilirubin; Blood Pressure; Confounding Factors, Epidemiologic; Health Behavior; Humans; Hypertension; Nutrition Surveys; Oxidative Stress; Prevalence; Random Allocation; Reproducibility of Results; Risk Factors; Sex Factors; Socioeconomic Factors
PubMed: 25541554
DOI: 10.1093/ije/dyu242 -
Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea.American Journal of Physiology. Heart... Sep 2018Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals... (Review)
Review
Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.
Topics: Animals; Bilirubin; Cardiovascular Diseases; Cardiovascular System; Humans; Hyperbilirubinemia
PubMed: 29600900
DOI: 10.1152/ajpheart.00417.2017 -
Journal of Clinical Laboratory Analysis Nov 2017Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as...
BACKGROUND
Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as immunomodulator. Increased evidence shows that bilirubin should be a protective factor for autoimmune disease. However, the relationship between bilirubin and RA remain unclear.
METHODS
We analyzed serum bilirubin levels and other laboratory and clinical data in 130 RA patients (35 patients without any complications), 81 osteoarthritis (OA) patients and 96 healthy controls.
RESULTS
Binary logistic regression adjusted by age and gender revealed that the levels of serum total, indirect bilirubin were significantly lower in RA patients, when compared with healthy controls (P=.015, OR=0.767, 95% CI=0.619-0.951; P=.010, OR=0.664, 95% CI=0.487-0.906, respectively) or OA patients (P=.000, OR=0.763, 95% CI=0.661-0.882; P=.000, OR=0.656, 95% CI=0.532-0.808, respectively). A reduced trend of levels of bilirubin has been detected along with increased disease activity, despite with no significance (P>.05). Spearman rank test further demonstrated that IgG and ESR were negative associated with total, indirect bilirubin, and albumin, prealbumin, APOA, HDL-C were positively associated with bilirubin.
CONCLUSIONS
In conclusion, the levels of serum bilirubins were decreased in RA, and decreased levels could be associated with IgG, albumin and inflammatory marker ESR.
Topics: Adult; Aged; Arthritis, Rheumatoid; Bilirubin; Biomarkers; Case-Control Studies; Female; Humans; Logistic Models; Male; Middle Aged; Osteoarthritis; Oxidative Stress
PubMed: 28177535
DOI: 10.1002/jcla.22118 -
Molecules (Basel, Switzerland) Mar 2023In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the... (Review)
Review
In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly rather than configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either or configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds.
Topics: Biliverdine; Bilirubin; Circular Dichroism; Molecular Conformation; Vibration; Stereoisomerism
PubMed: 36985535
DOI: 10.3390/molecules28062564 -
Acta Physiologica (Oxford, England) Aug 2017
Topics: Aging; Animals; Bilirubin; Heart; Humans
PubMed: 28296151
DOI: 10.1111/apha.12873 -
Thorax Nov 2020Moderately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect...
BACKGROUND
Moderately raised serum bilirubin levels are associated with lower rates of lung cancer, particularly among smokers. It is not known whether these relationships reflect antioxidant properties or residual confounding.
OBJECTIVE
This study aimed to investigate potential causal relationships between serum total bilirubin and lung cancer incidence using one-sample Mendelian randomisation (MR) and UK Biobank.
METHODS
We instrumented serum total bilirubin level using two variants (rs887829 and rs4149056) that together explain ~40% of population-level variability and are linked to mild hereditary hyperbilirubinaemia. Lung cancer events occurring after recruitment were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and rate differences per 10 000 person-years (PYs) by smoking status were estimated.
RESULTS
We included 377 294 participants (median bilirubin 8.1 μmol/L (IQR 6.4-10.4)) and 2002 lung cancer events in the MR analysis. Each 5 μmol/L increase in observed bilirubin levels was associated with 1.2/10 000 PY decrease (95% CI 0.7 to 1.8) in lung cancer incidence. The corresponding MR estimate was a decrease of 0.8/10 000 PY (95% CI 0.1 to 1.4). The strongest associations were in current smokers where a 5 μmol/L increase in observed bilirubin levels was associated with a decrease in lung cancer incidence of 10.2/10 000 PY (95% CI 5.5 to 15.0) and an MR estimate of 6.4/10 000 PY (95% CI 1.4 to 11.5). For heavy smokers (≥20/day), the MR estimate was an incidence decrease of 23.1/10 000 PY (95% CI 7.3 to 38.9). There was no association in never smokers and no mediation by respiratory function.
CONCLUSION
Genetically raised serum bilirubin, common across human populations, may protect people exposed to high levels of smoke oxidants against lung cancers.
Topics: Adult; Aged; Bilirubin; Biological Specimen Banks; Causality; Female; Humans; Incidence; Lung Neoplasms; Male; Mendelian Randomization Analysis; Middle Aged; Registries; Smoking; United Kingdom
PubMed: 32855344
DOI: 10.1136/thoraxjnl-2020-214756 -
Developmental Medicine and Child... Mar 2017
Topics: Bilirubin; Humans
PubMed: 27786370
DOI: 10.1111/dmcn.13303