| The effects of the phytoestrogenic isoflavone genistein on the hepatic disposition of preformed and hepatically generated gemfibrozil 1-O-acyl glucuronide in the isolated perfused rat liver. | |
| | |
MedLine Citation:
|
PMID: 14607027 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Foods and complementary medicines contain phytoestrogenic isoflavones such as genistein, which undergo hepatic glucuronidation and excretion into bile and can potentially interfere with the hepatic elimination of other compounds. To investigate this potential, livers from Sprague-Dawley rats were perfused in single-pass mode with preformed gemfibrozil 1-O-acyl glucuronide (GG) (1 microM, n = 12) for 60 min followed by a 30-min washout phase, or with gemfibrozil (1 microM, n = 10) for 120 min. Half of each group of livers were co-perfused with genistein (10 microM) throughout the experiment. Perfusate and bile were analyzed for GG and gemfibrozil by HPLC. Co-perfusion with genistein significantly (P< 0.05) decreased the biliary extraction ratio of preformed GG from a mean of 0.82 to 0.65 and the first-order rate constant for transport of GG into bile from 0.054 +/- 0.010 to 0.032 +/- 0.008 min(-1), but increased the first-order rate constant for sinusoidal efflux of GG from 0.128 +/- 0.023 to 0.227 +/- 0.078 min(-1). Co-perfusion with genistein also significantly decreased the biliary extraction ratio of hepatically generated GG from 0.95 +/- 0.01 to 0.83 +/- 0.05. The findings confirm that genistein increases the potential for hepatic and systemic exposure to hepatically generated glucuronides, which may be important for patients on conventional drugs who consume isoflavones. |
| | |
Authors:
|
Anthony N Lucas; Léonie R Brogan; Roger L Nation; Robert W Milne; Allan M Evans; David M Shackleford |
Related Documents
:
|
10710507 - Catabolism of arginine and ornithine in the perfused rat liver: effect of dietary prote... 2967257 - Constant-pressure perfusion on the isolated rat liver: local oxygen supply and metaboli... 17725817 - Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver i... 6376897 - Perfusion preservation of cadaver rat pancreas: i. morphological observation and biolog... 1611527 - Cortical hypoperfusion following spreading depression is not altered by tirilazad mesyl... 16867157 - Increased levels of ige and autoreactive, polyreactive igg in wild rodents: implication... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Journal of pharmacy and pharmacology Volume: 55 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2003 Oct |
Date Detail:
|
Created Date: 2003-11-10 Completed Date: 2004-02-10 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
|
Languages: eng Pagination: 1433-9 Citation Subset: IM |
Affiliation:
|
Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, SA 5000, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Chemotherapy, Cancer, Regional Perfusion Drug Interactions Enzyme Inhibitors / pharmacology* Gemfibrozil / analogs & derivatives*, pharmacokinetics* Genistein / pharmacology* Glucuronates / pharmacokinetics* Kinetics Liver / chemistry Male Organ Culture Techniques Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Glucuronates; 25812-30-0/Gemfibrozil; 446-72-0/Genistein; 91683-38-4/gemfibrozil 1-O-acylglucuronide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peroxynitrite scavenging activity of lithospermate B from Salvia miltiorrhiza.
Next Document: Intratumoural chemotherapy with 5-fluorouracil for palliation of bronchial cancer in patients with s...