• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    The Utilization of Cellular and Subcellular Liver Models to Assess Glucronidation of Bisphenol A in Animals and Humans

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_etd_1493_sip1_m.pdf
    Size:
    893.1Kb
    Format:
    PDF
    Description:
    azu_etd_1493_sip1_m.pdf
    Download
    Author
    Kuester, Robert
    Issue Date
    2006
    Advisor
    Sipes, I. Glenn
    Committee Chair
    Sipes, I. Glenn
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Bisphenol A (BPA) is a phenolic compound with industrial and commercial uses. In the liver BPA undergoes extensive metabolism and is eliminated primarily as a glucuronide conjugate. This dissertation compared the metabolism BPA in hepatocytes (HC) to those observed with hepatic microsomes (mics). These values were then scaled to predict the total hepatic metabolic clearance (CLmet ) and compared to human hepatic blood flow (HBF, 20 ml/min/kg).The mean CLint for human HC was 126±63 and 149±72 ml/min/kg for male female HC, respectively. When CLint was scaled to account for HBF, the estimated CLmet values were 16.9 and 17.3 ml/min/kg for male and female HC, respectively.To understand how age, gender, strain and species affects BPA glucuronidation, CLint of BPA was determined from incubations of mics isolated from adult male and female Sprague Dawley (SD) rats (77-day old), newborn (21- day), fetal (gestational day 19 [GD-19]) SD rats. Additional incubations were conducted with mics from adult F-344 rats, CF1 mice and humans. All specimens (HC and mics) were incubated with various concentrations of [14C]-BPA and the formation of a BPA-glucuronide (predominant metabolite) followed Michaelis Menton kinetics.Mics from adult F-344 rats formed BPA glucuronide similar those obtained from SD rats. Fetal mics showed a decreased capacity to glucuronidate BPA as compared to mics of adult rats. These data demonstrate that the glucuronsyltransferase activity responsible for BPA metabolism is developed before GD-19 and increases soon after birth. The rates of BPA-glucuronide formation (in vitro) were observed to be related to body mass with the mouse having the largest CLint and humans having the lowest.The differences in glucuronidation rates observed in vitro were minimized when values were scaled to account for the total metabolic capacity of the liver. These estimated CLmet values represent 85% to 90% of HBF which explained the very low levels of free BPA observed in the blood of human volunteers who ingested BPA (5 mg/person). Thus, hepatic glucuronidation is an efficient "first pass" mechanism which greatly reduces systemic exposure to BPA ingested orally.
    Type
    text
    Electronic Dissertation
    Degree Name
    PhD
    Degree Level
    doctoral
    Degree Program
    Pharmacology & Toxicology
    Graduate College
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.