| Human hepatocyte--a model for toxicological studies. Functional and biochemical characterization. | |
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MedLine Citation:
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PMID: 11156444 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Isolated human hepatocytes (HH) are an accepted model for in vitro experiments for testing liver function and xenobiotic metabolism. Preferred over more traditional animal hepatocyte model used in toxicological studies, it is the model of choice when substances undergoing biotransformation in man are investigated. The aim of this study was to optimize isolation and culture conditions for HH primary culture with regard to cell yield, viability, and metabolic activity, and to evaluate the suitability of donor samples for toxicology experiments. Cell viability, total cytochrome P450 (CYP) content, CYP3A4, CYP1A2 activity, and finally mixed ethoxycoumarin-O-deethylase (ECOD) activity were parameters measured in order to characterize the isolated HH. The quality of the primary cultures, stable and functional for a seven-day period following 24 hour stabilization, was assessed by lactate dehydrogenase (LDH) leakage and response to the model toxin tert-butylhydroperoxide (tBH) and to silybinin, a model cytoprotective substance. Based on HH obtained from livers of five multiorgan donors (average age 44.8 years, three males and two females), the individual variability of donors needs to be considered in evaluating cultures focussing on clinical liver tests. Greater sensitivity to toxins and silybinin was found in the hepatocyte culture from one donor with higher aminotransferase activity. In another case, higher serum bilirubin appeared to be linked to higher ECOD activity. Our conclusion is that values of clinical liver tests ought to suggest a healthy organ thus eliminating previous hepatocyte damage, the crucial factor of primary culture stability and functioning. |
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Authors:
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M Modrianský; J Ulrichová; P Bachleda; P Anzenbacher; E Anzenbacherová; D Walterová; V Simánek |
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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: General physiology and biophysics Volume: 19 ISSN: 0231-5882 ISO Abbreviation: Gen. Physiol. Biophys. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2001-01-11 Completed Date: 2001-03-29 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8400604 Medline TA: Gen Physiol Biophys Country: Slovakia |
Other Details:
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Languages: eng Pagination: 223-35 Citation Subset: IM |
Affiliation:
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Department of Medical Chemistry and Biochemistry, Medical Faculty, Palacký University, Olomouc, Czech Republic. oregon@tunw.upol.cz |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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7-Alkoxycoumarin O-Dealkylase
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metabolism Adult Antioxidants / toxicity Calcium Channel Blockers / toxicity Cell Culture Techniques / methods* Cells, Cultured Cytochrome P-450 CYP1A2 / metabolism Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System / metabolism Enzyme Inhibitors / toxicity Female Hepatocytes / chemistry*, drug effects*, physiology* Humans L-Lactate Dehydrogenase / metabolism, toxicity Liver / drug effects, metabolism Male Microsomes, Liver / drug effects Middle Aged Mixed Function Oxygenases / metabolism Nifedipine / toxicity Rifampin / toxicity Silymarin / toxicity Time Factors Toxicity Tests / methods tert-Butylhydroperoxide / toxicity |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Calcium Channel Blockers; 0/Enzyme Inhibitors; 0/Silymarin; 13292-46-1/Rifampin; 21829-25-4/Nifedipine; 75-91-2/tert-Butylhydroperoxide; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.14.13.-/7-Alkoxycoumarin O-Dealkylase; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/CYP3A protein, human; EC 1.14.14.1/Cytochrome P-450 CYP1A2; EC 1.14.14.1/Cytochrome P-450 CYP3A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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