title: Beyond plasma bilirubin: the effects of phototherapy and albumin on brain bilirubin levels in Gunn rats.
abstract: OBJECTIVE
  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.
  
  
  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 UCB(free) and brain bilirubin by 88% and 67%, respectively (p<0.001). In the acute model, adjunct HSA also increased the efficacy of phototherapy; it decreased plasma UCB(free) by 76% (p<0.001) 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.
  
  
  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 UCB(free) in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice.
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, Beatrix Children's Hospital - University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Frans J C
authors.initials: FJ
authors.lastname: Cuperus
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Schreuder
authors.forename: Deirdre E
authors.initials: DE
authors.lastname: van Imhoff
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Jana
authors.initials: J
authors.lastname: Vanikova
authors.forename: Renata
authors.initials: R
authors.lastname: Konickova
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ahlfors
authors.forename: Christian V
authors.initials: CV
authors.lastname: Hulzebos
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
mesh_terms: D000208:Acute Disease; D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D003414:Crigler-Najjar Syndrome / Q000378:metabolism* / Q000628:therapy*; D004195:Disease Models, Animal; D006932:Hyperbilirubinemia / Q000378:metabolism / Q000628:therapy; D007565:Jaundice / Q000378:metabolism / Q000628:therapy; D008297:Male; D010789:Phototherapy / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011911:Rats, Gunn
chemical_list: D000418:Albumins; D001663:Bilirubin