| Age-related pseudocapillarization of the liver sinusoidal endothelium impairs the hepatic clearance of acetaminophen in rats. | |
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MedLine Citation:
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PMID: 21300741 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer (14)C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p < .05). In old age, there was significant reduction of the intercompartmental rate constant k(1) (0.34 ± 0.10 s(-1), old; 0.61 ± 0.38 s(-1), young; p < .05) and the permeability-surface area product for the transfer of acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p < .005). There was no difference in k(3), the measure of sequestration of acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. |
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Authors:
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Sarah J Mitchell; Aniko Huizer-Pajkos; Victoria C Cogger; Andrew J McLachlan; David G Le Couteur; Brett Jones; Rafael de Cabo; Sarah N Hilmer |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2011-02-07 |
Journal Detail:
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Title: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 66 ISSN: 1758-535X ISO Abbreviation: J. Gerontol. A Biol. Sci. Med. Sci. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-14 Completed Date: 2011-06-02 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 9502837 Medline TA: J Gerontol A Biol Sci Med Sci Country: United States |
Other Details:
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Languages: eng Pagination: 400-8 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia. sarah.mitchell@sydney.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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pharmacokinetics* Aging Analgesics, Non-Narcotic / pharmacokinetics* Animals Antipyretics / pharmacokinetics* Endothelium / metabolism Indicator Dilution Techniques Liver / blood supply, metabolism*, ultrastructure Male Microscopy, Electron, Scanning Rats Rats, Inbred F344 |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Non-Narcotic; 0/Antipyretics; 103-90-2/Acetaminophen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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