title: Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups.
abstract: BACKGROUND
  Few data exist on regional brain bilirubin content in the neonatal period when acute bilirubin-induced neurologic damage (BIND) may occur, and no information is available on regional brain expression of cytochrome P450 monooxygenases (Cyps) that oxidize bilirubin.
  
  
  METHODS
  Bilirubin content was analyzed by high-performance liquid chromatography and Cyp1a1, 1a2, and 2a3 mRNA expression was analyzed by quantitative PCR (qPCR) in cortex (Cx), cerebellum (Cll), superior colliculi (SC), and inferior colliculi (IC) of 17-d-old hyperbilirubinemic (jj) Gunn rat pups before and after administration of sulphadimethoxine to acutely displace bilirubin from plasma albumin.
  
  
  RESULTS
  There was no difference in bilirubin content among brain regions in untreated rats. After intraperitoneal sulphadimethoxine, bilirubin content peaked at fourfold in Cx and SC at 1 h; but at 11- to 13-fold in Cll and IC at 24 h; returning to control levels at 72 h. The Cyp mRNA peaked at 30-70 times control at 1 h in Cx and SC, but at 3-9 times control at 24 h in Cll and IC.
  
  
  CONCLUSIONS
  The close relationship in distinct brain regions between the extent of bilirubin accumulation and induction of mRNA of Cyps suggests Cyps may have a role in protecting selected brain areas from bilirubin neurotoxicity.
authors.affiliation: Fondazione Italiana Fegato (Italian Liver Foundation), Trieste, Italy. silvia.gazzin@csf.units.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Gazzin
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Zelenka
authors.forename: Lucie
authors.initials: L
authors.lastname: Zdrahalova
authors.forename: Renata
authors.initials: R
authors.lastname: Konickova
authors.forename: Carlos Coda
authors.initials: CC
authors.lastname: Zabetta
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Giraudi
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Berengeno
authors.forename: Alan
authors.initials: A
authors.lastname: Raseni
authors.forename: Maria C
authors.initials: MC
authors.lastname: Robert
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiribelli
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D007565:Jaundice / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011911:Rats, Gunn; D013412:Sulfadimethoxine / Q000494:pharmacology; D013477:Superior Colliculi / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000418:Albumins; D001189:Aryl Hydrocarbon Hydroxylases; D001663:Bilirubin; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D013412:Sulfadimethoxine; C095122:multidrug resistance protein 3; C421109:multidrug resistance-associated protein 1