Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups

SILVIA GAZZIN; JAROSLAV ZELENKA; LUCIE ZDRAHALOVA; RENATA KONICKOVA; CARLOS CODA ZABETTA; PABLO J. GIRAUDI; ANDREA L. BERENGENO; ALAN RASENI; MARÍA C. ROBERT; LIBOR VITEK; CLAUDIO TIRIBELLI

PEDIATRIC RESEARCH

INT PEDIATRIC RESEARCH FOUNDATION, INC

Lugar: The Woodlands, Texas; Año: 2012 vol. 71 p. 653 - 660

0031-3998

Introduction: 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. Discussion: 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.