title: Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia.
abstract: Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99 - 34149 - Trieste, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Vodret
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99 - 34149 - Trieste, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bortolussi
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, Beatrix Children's Hospital-University Medical Center, Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Schreuder
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 2, Prague, 120 00, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Jašprová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 2, Prague, 120 00, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, Beatrix Children's Hospital-University Medical Center, Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99 - 34149 - Trieste, Italy.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Muro
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D002531:Cerebellum / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000097:blood / Q000150:complications*; D007567:Jaundice, Neonatal / Q000097:blood / Q000150:complications; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D010789:Phototherapy / Q000379:methods; D012709:Serum Albumin / Q000008:administration & dosage*
chemical_list: D012709:Serum Albumin; D001663:Bilirubin