Document Detail


The bioreactor with CYP3A4- and glutamine synthetase-introduced HepG2 cells: treatment of hepatic failure dog with diazepam overdosage.
MedLine Citation:
PMID:  16048486     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel recombinant human hepatic cell line, CYP3A4- and glutamine synthetase (GS, an enzyme which converts ammonium ion and glutamate to glutamine)-introduced HepG2 (HepG2-GS-CYP3A4), was established. Its usefulness in a large-scale culture with a circulatory bioreactor in vitro and in dog models of ischemic hepatic failure with acute diazepam (DZP, a substrate of CYP3A4) overdosage was further examined. HepG2-GS-CYP3A4 expressed about 9 times larger amounts of CYP3A4 protein than a control. After incubation with HepG2-GS-3A4 cells in a circulatory bioreactor for 24 h, ammonia and DZP concentrations in the culture medium significantly decreased by about 40%. Furthermore, this system improved the survival time and decreased serum concentrations of DZP, ammonia, and transaminase in dogs with ischemic hepatic failure plus acute DZP overdosage. The mean survival time with bioreactor with HepG2-GS-3A4 was 42.7 +/- 3.6 h, which was significantly longer than that without reactor, with reactor (no cells), and with HepG2-GS (23.4 +/- 2.8, 22.1 +/- 2.4, and 31 +/- 3.7 h, respectively). Therefore, it is concluded that this bioartificial liver could be a good tool for the treatment of dogs with hepatic failure and that it could potentially be a bridging procedure to liver transplantation.
Authors:
Ning Wang; Shuichi Tsuruoka; Hisashi Yamamoto; Shin Enosawa; Takeshi Omasa; Naohiro Sata; Toshiharu Matsumura; Hideo Nagai; Akio Fujimura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Artificial organs     Volume:  29     ISSN:  0160-564X     ISO Abbreviation:  Artif Organs     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-28     Completed Date:  2005-12-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7802778     Medline TA:  Artif Organs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  681-4     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bioreactors*
Cell Line
Cricetinae
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / metabolism*
Diazepam / administration & dosage,  adverse effects,  analysis
Dogs
Glutamate-Ammonia Ligase / metabolism*
Humans
Hypnotics and Sedatives / administration & dosage,  adverse effects,  analysis
Liver Failure / metabolism,  therapy*,  veterinary
Liver, Artificial*
Overdose
Chemical
Reg. No./Substance:
0/Hypnotics and Sedatives; 439-14-5/Diazepam; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/CYP3A protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 6.3.1.2/Glutamate-Ammonia Ligase

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


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