Abstract:
:Liver diseases are associated with a decrease in hepatic drug elimination, but there is evidence that cirrhosis does not result in uniform changes of cytochrome P450 (CYP) isoenzymes. The objective of this study was to determine the content and activity of four CYP isoenzymes in the bile duct ligation and carbon tetrachloride (CCl4)-induced models of cirrhosis. The hepatic content of CYP1A, CYP2C, CYP2E1, and CYP3A was measured by Western blot analysis. CYP activity in vivo was evaluated with breath tests using substrates specific for different isoenzymes: caffeine (CYP1A2), aminopyrine (CYP2C11), nitrosodimethylamine (CYP2E1), and erythromycin (CYP3A). Bile duct ligation resulted in biliary cirrhosis; CYP1A, CYP2C and CYP3A content was decreased and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas CYP2E1 content and the nitrosodimethylamine breath test were unchanged compared with controls. CCl4 treatment resulted in cirrhosis of varying severity as assessed from the decrease in liver weight and serum albumin. In rats with mild cirrhosis, CYP content was comparable with controls except for a decrease in CYP2C. The activity of CYPs was also unchanged except for an increase in CYP2E1 activity. In rats with more severe cirrhosis, the content of all four CYP isoenzymes and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas the nitrosodimethylamine breath test was unchanged. In both models of cirrhosis, there was a significant correlation between the breath tests results and the severity of cirrhosis as assessed from serum albumin levels. These results indicate that content and the catalytic activity of individual CYP enzymes are differentially altered by cirrhosis in the rat and also suggest that drug probes could be useful to assess hepatic functional reserve.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Bastien MC,Leblond F,Pichette V,Villeneuve JPsubject
Has Abstractpub_date
2000-11-01 00:00:00pages
912-9issue
11eissn
0008-4212issn
1205-7541journal_volume
78pub_type
杂志文章abstract::Androgens have been reported to stimulate progesterone production by granulosa cells of several species, and to act synergistically with FSH in stimulation of progesterone accumulation by rat granulosa cells. Studies were undertaken to examine the effect of androgens on FSH-stimulated progesterone production in cultur...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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doi:10.1139/y75-020
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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doi:10.1139/cjpp-76-12-1161
更新日期:1998-12-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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doi:10.1139/y79-096
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章,评审
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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