| Effects of choline-deprivation on paracetamol- or phenobarbital-induced rat liver metabolic response. | |
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MedLine Citation:
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PMID: 18798224 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Choline is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions in both humans and rodents. Various pathophysiological states have been linked to choline deprivation (CD). The aim of the present study was to determine the effect of CD upon biochemical, histological and metabolic alterations induced by drugs that affect hepatic functional integrity and various drug metabolizing systems via distinct mechanisms. For this purpose, paracetamol (ACET) or phenobarbital (PB) were administered to male Wistar rats that were fed with standard rodent chow (normally fed, NF) or underwent dietary CD. The administration of ACET increased the serum aspartate aminotransferase levels in NF rats, while CD restricted this increase. On the other hand, ACET suppressed alkaline phosphatase levels only in CD rats. Moreover, CD prevented the PB-induced increase of the mitotic activity of hepatocytes. The administration of ACET down-regulated CYP1A2 and CYP2B1 expression in CD rats, while up-regulating them in NF rats. The administration of PB suppressed CYP1A2 apoprotein levels in CD rats, whereas the drug had no effect on NF rats. The PB-induced up-regulation of CYP2B, CYP2E1 and CYP1A1 isozymes was markedly higher in CD than in NF rats. In addition, PB increased glutathione-S-transferase activity only in CD rats. Hepatic glutathione content (GSH) was suppressed by ACET in NF rats, whereas the drug increased GSH in CD rats. Our data suggest that CD has a significant impact on the hepatic metabolic functions, and in particular on those related to drug metabolism. Thus, CD may modify drug effectiveness and toxicity, as well as drug-drug interactions, particularly those related to ACET and PB. |
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Authors:
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Maria Konstandi; Dimitrios Segos; Panagiota Galanopoulou; Stamatios Theocharis; Apostolos Zarros; Matti A Lang; Marios Marselos; Charis Liapi |
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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: Journal of applied toxicology : JAT Volume: 29 ISSN: 1099-1263 ISO Abbreviation: J Appl Toxicol Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-12 Completed Date: 2009-07-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109495 Medline TA: J Appl Toxicol Country: England |
Other Details:
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Languages: eng Pagination: 101-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Medical School, University of Ioannina, Ioannina, Greece. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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pharmacology* Alanine Transaminase / blood Alkaline Phosphatase / metabolism Analgesics, Non-Narcotic / pharmacology* Animals Aspartate Aminotransferases / blood Body Weight / drug effects Choline Deficiency / metabolism* Cytochrome P-450 CYP1A1 / metabolism Cytochrome P-450 CYP1A2 / metabolism Cytochrome P-450 CYP2B1 / metabolism Cytochrome P-450 CYP2E1 / metabolism Gene Expression Regulation, Enzymologic / drug effects Glutathione / metabolism Glutathione Transferase / metabolism Liver / drug effects*, enzymology Male Microsomes, Liver / enzymology, metabolism Phenobarbital / pharmacology* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Non-Narcotic; 103-90-2/Acetaminophen; 50-06-6/Phenobarbital; 70-18-8/Glutathione; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/Cytochrome P-450 CYP1A2; EC 1.14.14.1/Cytochrome P-450 CYP2B1; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 2.5.1.18/Glutathione Transferase; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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