Beyond plasma bilirubin: the effects of herapy and albumin on brain bilirubin levels in Gunn rats
Autor: | Charles E. Ahlfors, Christian V. Hulzebos, Renata Koníčková, Henkjan J. Verkade, Jana Vanikova, Andrea B. Schreuder, Libor Vítek, Deirdre E. van Imhoff, Frans J C Cuperus |
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Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM), Reproductive Origins of Adult Health and Disease (ROAHD) |
Rok vydání: | 2013 |
Předmět: |
Male
medicine.medical_specialty KERNICTERUS Bilirubin Crigler–Najjar syndrome UNCONJUGATED HYPERBILIRUBINEMIA Rats Gunn Jaundice INFANTS EXCHANGE TRANSFUSIONS chemistry.chemical_compound Random Allocation Internal medicine Albumins UNBOUND BILIRUBIN Medicine Animals INFUSION THERAPY Molecular gastro-enterology and hepatology [IGMD 2] Unconjugated hyperbilirubinemia Hyperbilirubinemia INTENSIVE PHOTOTHERAPY Hepatology business.industry Albumin Brain ENCEPHALOPATHY Phototherapy medicine.disease Gunn rat Rats Disease Models Animal Endocrinology chemistry NEONATAL JAUNDICE Free fraction Anesthesia embryonic structures Acute Disease Chronic Disease Kernicterus medicine.symptom business CRIGLER-NAJJAR SYNDROME |
Zdroj: | Journal of Hepatology, 58, pp. 134-140 Journal of Hepatology, 58, 134-140 Journal of Hepatology, 58(1), 134-140. ELSEVIER SCIENCE BV |
ISSN: | 0168-8278 |
Popis: | 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 (UCB(free)), the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCB(free) fraction, and thus decrease bilirubin accumulation in the brain.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.In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCB(free) and brain bilirubin by 88% and 67%, respectively (p0.001). In the acute model, adjunct HSA also increased the efficacy of phototherapy; it decreased plasma UCB(free) by 76% (p0.001) and completely prevented the hemolysis-induced deposition of bilirubin in the brain. Phototherapy alone failed to prevent the deposition of bilirubin in the brain during acute hemolytic jaundice.We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCB(free) in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice. |
Databáze: | OpenAIRE |
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