Document Detail


Comparative effect of colchicine and colchiceine on cytotoxicity and CYP gene expression in primary human hepatocytes.
MedLine Citation:
PMID:  12020594     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aims of the present study were (1) to determine the cytotoxicity of colchiceine (EIN) in comparison with that of colchicine (COL); (2) to evaluate the effect of EIN on cytochrome P450 (CYP) expression and activity. Primary human hepatocytes were the model of choice for cytotoxicity and CYP expression experiments. LDH leakage and albumin secretion served as cytotoxicity parameters. EIN was less toxic than COL based on both parameters within the concentration range 1-100 microM. 10 microM concentration of EIN did not induce the expression of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 isoforms, which were evaluated at the levels of mRNAs, proteins and specific activities in culture. EIN in concentrations up to 200 microM had no effect on marker activities of CYP1A2, 2C9, 2E1 and 3A4 in human liver microsomes. It was concluded that EIN in concentrations up to 10 microM is not cytotoxic in primary human hepatocytes as revealed by albumin secretion and LDH leakage. Possible drug-drug interactions of EIN due to effects on cytochromes P4501A2, 2C9, 2E1 and 3A4 isoforms are unlikely because inhibition/induction studies show any lack of such effects. As EIN was shown to have better antifibrotic properties than COL (European Journal of Clinical Investigation 1997, 2, 77), it can be used as a COL substitute with anticipated fewer side-effects.
Authors:
Z Dvorak; J Ulrichova; L Pichard-Garcia; M Modriansky; P Maurel
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  16     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-21     Completed Date:  2002-11-14     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  219-27     Citation Subset:  IM    
Affiliation:
Institute of Medical Chemistry and Biochemistry, Medical Faculty, Palacky University Olomouc, Hnevotinska 3, 77515 OLOMOUC, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Albumins / secretion
Blotting, Northern
Blotting, Western
Cell Survival / drug effects
Cells, Cultured
Colchicine / analogs & derivatives*,  toxicity*
Cytochrome P-450 Enzyme System / biosynthesis,  genetics*
Dose-Response Relationship, Drug
Gene Expression
Hepatocytes / drug effects*,  enzymology
Humans
L-Lactate Dehydrogenase / metabolism
Microsomes, Liver / drug effects,  enzymology
Protein Isoforms
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/Albumins; 0/Protein Isoforms; 0/RNA, Messenger; 477-27-0/colchiceine; 64-86-8/Colchicine; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.1.1.27/L-Lactate Dehydrogenase

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


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