Document Detail

Subcellular localization of bilirubin in rat brain after in vivo i.v. administration of [3H]bilirubin.
MedLine Citation:
PMID:  11158514     Owner:  NLM     Status:  MEDLINE    
Bilirubin appears to be toxic in vitro to several cellular functions localized to different subcellular compartments. It would therefore be useful to know what concentrations of bilirubin might be found in cell organelles in vivo. Rats were anesthetized and allocated to one of three groups: control, hypercarbia, and hyperosmolality. Each rat received a 5-min bolus dose of bilirubin 50 mg/kg i.v. (containing approximately 200 microCi [(3)H]bilirubin). Rats were killed 10 or 30 min after the start of the bilirubin infusion. Each brain was homogenized, and subcellular fractions were isolated by high-speed gradient centrifugation in sucrose media. The gradients were separated into aliquots of 2 mL, and the protein content was determined in each aliquot. Radioactivity was determined by scintillation counting, and the content of bilirubin per milligram of protein was calculated. Statistical comparisons were performed with Kruskal-Wallis nonparametric ANOVA. There were highly significant differences in bilirubin content per milligram of protein among subcellular compartments in all groups and at both time points. In all groups there were relatively high concentrations of bilirubin in the myelin fraction, an interesting observation in light of the theory that membranes are the primary target of bilirubin toxicity. The very high concentration of bilirubin relative to protein in cytoplasm, ribosomes, and mitochondria in the hyperosmolar group are also notable in light of data from hyperbilirubinemic animals in which changes in electrophysiology or energy metabolism only appeared after hyperosmolar opening of the blood-brain barrier. The present data may be useful in planning in vitro studies of bilirubin toxicity in cell organelles.
T Hansen; S Tommarello; J Allen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pediatric research     Volume:  49     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-12     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-7     Citation Subset:  IM    
Department of Anesthesiology and Critical Care Medicine, Children's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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MeSH Terms
Bilirubin / administration & dosage,  metabolism*
Brain / metabolism*
Infusions, Intravenous
Rats, Sprague-Dawley
Subcellular Fractions / metabolism*
Reg. No./Substance:
10028-17-8/Tritium; 635-65-4/Bilirubin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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