Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

Bin‐Nun, Alona; Mimouni, Francis; Kasirer, Yair; Schors, Irina; Schimmel, Michael S.; Kaplan, Michael; Hammerman, Cathy

doi:10.1055/s-0038-1641746

Cited by 11 publications

(13 citation statements)

References 20 publications

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“…As reviewed by Fujiwara et Al. [ 75 ], similar data are present also in neonates [ 72 , 73 , 74 ], where a close association between the plasma bilirubin concentration and the plasma antioxidant capacity has been reported [ 75 ], with icteric neonates showing a favourable plasma antioxidant capacity, that phototherapy worsened [ 173 ]. After more than a century, this supports the speculation that the production of UCB from BV, an unnecessary energy-consuming reaction, is motivated by the benefits of having higher antioxidant defense.…”

Section: The Yellow Players (Yp)supporting

confidence: 61%

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

et al. 2020

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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.

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Section: The Yellow Players (Yp)supporting

confidence: 61%

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

et al. 2020

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“…However, accumulating evidence indicates that early physiological increases in serum bilirubin levels in neonates may provide a protective antioxidant defense mechanism to compensate for otherwise deficient antioxidant enzymes, particularly in neonates with increased susceptibility to ischemia/reperfusion injury, such as infants with HIE [7]. In our clinical practice, patients with HIE were less likely to need or did not need phototherapy, and we speculate that bilirubin metabolism may be affected by HIE.…”

Section: Introductionmentioning

confidence: 88%

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy

et al. 2019

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Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

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“…2,3 Bilirubin is a natural antioxidant, and it presumably can protect the body from oxidative stress following birth. 2,3 Some studies have found that serum bilirubin levels following neonatal hypoxic-ischemic injury were lower than those of healthy controls. [3][4][5] These results can be explained by the hypothesis that bilirubin is consumed by scavenging free radicals following the hypoxic event.…”

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confidence: 99%

“…2,3 Some studies have found that serum bilirubin levels following neonatal hypoxic-ischemic injury were lower than those of healthy controls. [3][4][5] These results can be explained by the hypothesis that bilirubin is consumed by scavenging free radicals following the hypoxic event. [3][4][5] We aimed to investigate the effect of the severity of hypoxic injury on bilirubin levels to clarify this aspect of the physiological role of bilirubin.…”

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confidence: 99%

“…[3][4][5] These results can be explained by the hypothesis that bilirubin is consumed by scavenging free radicals following the hypoxic event. [3][4][5] We aimed to investigate the effect of the severity of hypoxic injury on bilirubin levels to clarify this aspect of the physiological role of bilirubin. To assess the severity of hypoxic injury, we used lactate as a biomarker for systemic hypoxia for the following reasons: it is produced during anaerobic metabolism when there is inadequate tissue oxygen delivery, 6 its level correlates with disease severity, 7 and postnatal lactate is an outcome predictor in asphyxiated newborns.…”

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confidence: 99%

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The Relationship between Serum Total Bilirubin and Severity of Hypoxic Injury in Neonatal Hypoxic–Ischemic Encephalopathy

et al. 2020

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Introduction Bilirubin has been found to be a natural antioxidant protecting the body from oxidative stress. This study aims to investigate the severity of neonatal hypoxic injury on bilirubin levels to clarify the physiological role of bilirubin. Study Design Using lactate as a biomarker for the severity of hypoxic injury, we retrospectively analyzed the association of admission lactate levels on serum total bilirubin (TB) levels following birth in neonates with hypoxic–ischemic encephalopathy (HIE). We created a univariate linear regression model to predict TB using the admission lactate level as a predictor. We also performed a multivariate linear regression analysis to predict TB with admission lactate levels that included phenobarbital cumulative dosage, admission hematocrit, and subgaleal hemorrhage as predictor variables. Results A total of 86 patients were studied. Admission lactate levels had a significant negative effect on TB from admission to 3 days of life. The standardized regression coefficient for admission lactate on TB was −0.37 (admission), −0.42 (day 1), −0.32 (day 2), and −0.28 (day 3). A similar negative effect of admission lactate on TB levels was also observed in the multivariate linear regression model even after controlling for the other variables. Conclusion These results are consistent with the hypothesis that bilirubin functions as an antioxidant in vivo, and is consumed by scavenging free radicals in proportion to the severity of hypoxic injury. Key Points

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Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

Abstract: Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.

Cited by 11 publications

References 20 publications

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

The Role of Bilirubin and the Other “Yellow Players” in Neurodegenerative Diseases

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy

The Relationship between Serum Total Bilirubin and Severity of Hypoxic Injury in Neonatal Hypoxic–Ischemic Encephalopathy

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