Document Detail


Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid.
MedLine Citation:
PMID:  11322201     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Unconjugated bilirubin (UCB) can be neurotoxic in jaundiced neonates and in patients with Crigler-Najjar syndrome. UCB toxicity may culminate in cell death, however, the occurrence of apoptosis has never been investigated. Ursodeoxycholic acid (UDCA) is a strong modulator of the apoptotic threshold in both hepatic and nonhepatic cells. The aims of this study were to determine whether apoptosis plays a role in neural cell death induced by UCB, and to investigate the ability of UDCA to prevent cell death. METHODS: Cultured rat astrocytes were incubated with UCB (17 and 86 microM) plus albumin (5.7 and 28.7 microM) for 4-22 h. In addition, astrocytes and neurones were treated with either UCB, 50 microM UDCA, or their combination for 4 h. Cultures were scored for nonviable cells by trypan blue dye exclusion. Apoptosis was assessed by Hoechst staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling assay. RESULTS: UCB induced a concentration- and time-dependent decrease in astrocyte viability. Apoptosis was 4- and 7-fold increased after 4 h exposure to 17 and 86 microM UCB, respectively (P < 0.01). UDCA reduced apoptosis to <7%, which represents a appoximately 60% protection (P < 0.01). Cholic acid was not protective, and chenodeoxyholic acid aggravated UCB toxicity (P < 0.05). Finally, neurones showed a 1.5-fold greater sensitivity than astrocytes to UCB, while UDCA was still protective. CONCLUSIONS: UCB is toxic to both astrocytes and neurones, causing cell death through an apoptotic process. Moreover, UDCA inhibits UCB-induced apoptosis in neural cells and this could not be mimicked by other bile acids.
Authors:
R F Silva; C M Rodrigues; D Brites
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  34     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-26     Completed Date:  2001-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  402-8     Citation Subset:  IM    
Affiliation:
Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Astrocytes / drug effects,  physiology
Bile Acids and Salts / physiology
Bilirubin / pharmacology*,  poisoning
Cells, Cultured
Chenodeoxycholic Acid / pharmacology*
Neurons / drug effects*,  physiology*
Rats
Rats, Wistar
Ursodeoxycholic Acid / pharmacology*
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 128-13-2/Ursodeoxycholic Acid; 474-25-9/Chenodeoxycholic Acid; 635-65-4/Bilirubin
Comments/Corrections
Comment In:
J Hepatol. 2001 Mar;34(3):467-70   [PMID:  11322210 ]

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