Beyond plasma bilirubin: The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats

Frans J. C. Cuperus; Andrea B. Schreuder; Deirdre E. van Imhoff; Libor Vitek; Jana Vanikova; Renata Konickova; Charles E. Ahlfors; Christian V. Hulzebos; Henkjan J. Verkade

doi:10.1016/j.jhep.2012.08.011

Beyond plasma bilirubin: The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats

Frans J. C. Cuperus, Andrea B. Schreuder, Deirdre E. van Imhoff, Libor Vitek, Jana Vanikova, Renata Konickova, Charles E. Ahlfors, Christian V. Hulzebos, Henkjan J. Verkade^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

Abstract

Background & Aims: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCBfree) the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCBfree fraction, and thus decrease bilirubin accumulation in the brain.

Methods: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy + HSA.

Results: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCBfree and brain bilirubin by 88% and 67%, respectively (p

Conclusions: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCBfree in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	134-140
Number of pages	7
Journal	Journal of Hepatology
Volume	58
Issue number	1
DOIs	https://doi.org/10.1016/j.jhep.2012.08.011
Publication status	Published - Jan-2013

Keywords

Unconjugated hyperbilirubinemia
Phototherapy
Albumin
Brain
Gunn rat
CRIGLER-NAJJAR SYNDROME
UNBOUND BILIRUBIN
NEONATAL JAUNDICE
UNCONJUGATED HYPERBILIRUBINEMIA
INTENSIVE PHOTOTHERAPY
EXCHANGE TRANSFUSIONS
INFUSION THERAPY
KERNICTERUS
INFANTS
ENCEPHALOPATHY

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Beyond plasma bilirubin: The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats
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@article{91222c37a9b04d069148c7137b86e1c9,

title = "Beyond plasma bilirubin: The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats",

abstract = "Background & Aims: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCBfree) the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCBfree fraction, and thus decrease bilirubin accumulation in the brain.Methods: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy + HSA.Results: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCBfree and brain bilirubin by 88% and 67%, respectively (pConclusions: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCBfree in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",

keywords = "Unconjugated hyperbilirubinemia, Phototherapy, Albumin, Brain, Gunn rat, CRIGLER-NAJJAR SYNDROME, UNBOUND BILIRUBIN, NEONATAL JAUNDICE, UNCONJUGATED HYPERBILIRUBINEMIA, INTENSIVE PHOTOTHERAPY, EXCHANGE TRANSFUSIONS, INFUSION THERAPY, KERNICTERUS, INFANTS, ENCEPHALOPATHY",

author = "Cuperus, {Frans J. C.} and Schreuder, {Andrea B.} and {van Imhoff}, {Deirdre E.} and Libor Vitek and Jana Vanikova and Renata Konickova and Ahlfors, {Charles E.} and Hulzebos, {Christian V.} and Verkade, {Henkjan J.}",

year = "2013",

month = jan,

doi = "10.1016/j.jhep.2012.08.011",

language = "English",

volume = "58",

pages = "134--140",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "ELSEVIER SCIENCE BV",

number = "1",

}

TY - JOUR

T1 - Beyond plasma bilirubin

T2 - The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats

AU - Cuperus, Frans J. C.

AU - Schreuder, Andrea B.

AU - van Imhoff, Deirdre E.

AU - Vitek, Libor

AU - Vanikova, Jana

AU - Konickova, Renata

AU - Ahlfors, Charles E.

AU - Hulzebos, Christian V.

AU - Verkade, Henkjan J.

PY - 2013/1

Y1 - 2013/1

N2 - Background & Aims: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCBfree) the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCBfree fraction, and thus decrease bilirubin accumulation in the brain.Methods: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy + HSA.Results: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCBfree and brain bilirubin by 88% and 67%, respectively (pConclusions: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCBfree in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AB - Background & Aims: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCBfree) the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCBfree fraction, and thus decrease bilirubin accumulation in the brain.Methods: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy + HSA.Results: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCBfree and brain bilirubin by 88% and 67%, respectively (pConclusions: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCBfree in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

KW - Unconjugated hyperbilirubinemia

KW - Phototherapy

KW - Albumin

KW - Brain

KW - Gunn rat

KW - CRIGLER-NAJJAR SYNDROME

KW - UNBOUND BILIRUBIN

KW - NEONATAL JAUNDICE

KW - UNCONJUGATED HYPERBILIRUBINEMIA

KW - INTENSIVE PHOTOTHERAPY

KW - EXCHANGE TRANSFUSIONS

KW - INFUSION THERAPY

KW - KERNICTERUS

KW - INFANTS

KW - ENCEPHALOPATHY

U2 - 10.1016/j.jhep.2012.08.011

DO - 10.1016/j.jhep.2012.08.011

M3 - Article

SN - 0168-8278

VL - 58

SP - 134

EP - 140

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 1

ER -