| The bioreactor with CYP3A4- and glutamine synthetase-introduced HepG2 cells: treatment of hepatic failure dog with diazepam overdosage. | |
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MedLine Citation:
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PMID: 16048486 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ning Wang; Shuichi Tsuruoka; Hisashi Yamamoto; Shin Enosawa; Takeshi Omasa; Naohiro Sata; Toshiharu Matsumura; Hideo Nagai; Akio Fujimura |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Artificial organs Volume: 29 ISSN: 0160-564X ISO Abbreviation: Artif Organs Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-28 Completed Date: 2005-12-07 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7802778 Medline TA: Artif Organs Country: United States |
Other Details:
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Languages: eng Pagination: 681-4 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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