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Research ArticleArticle

Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

Bradley W. Bolling, Michael H. Court, Jeffrey B. Blumberg and C.-Y. Oliver Chen
Drug Metabolism and Disposition August 2011, 39 (8) 1406-1414; DOI: https://doi.org/10.1124/dmd.111.038406
Bradley W. Bolling
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Michael H. Court
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Jeffrey B. Blumberg
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C.-Y. Oliver Chen
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Abstract

UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in three equidistant small intestine (SI) segments from 4-, 12-, 18-, and 28-month-old male Fischer 344 rats (n = 8/age) using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin was increased 3- to 9-fold from 4 months in the proximal and distal SI at 12 and 18 months. Likewise, at 30 μM quercetin, SI microsomal glucuronidation activity was increased with age: 4.8- and 3.9-fold greater at 18 months than at 4 months. Quercetin UGT regioselectivity was not changed by age. The distal SI preferentially catalyzed glucuronidation at the 7-position, whereas the proximal SI produced the greatest proportion of 4′- and 3′-conjugates. Enterocyte UGT content in different SI segments was not consistently changed with age. In the proximal SI, UGT1A increased 64 and 150% at 12 and 18 months and UGT1A1, UGT1A7, and UGT1A8 were also increased at 12 and 18 months. However, age-related changes in expression were inconsistent in the medial and distal segments. Microsomal rates of quercetin glucuronidation and UGT expression were positively correlated with UGT1A1 content for all pooled samples (r = 0.467) and at each age (r = 0.538–0.598). UGT1A7 was positively correlated with total, 7-O- and 3-O-quercetin glucuronidation at 18 months. Thus, age-related differences in UGT quercetin glucuronidation depend on intestinal segment, are more pronounced in the proximal and distal segments and may be partially related to UGT1A1 and UGT1A7 content.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants K12-GM074869, R01-GM061834]; and the U.S. Department of Agriculture/Agricultural Research Service [Cooperative Agreement 58-1950-7-707].

  • The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. All authors have no conflicts of interest.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.111.038406.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    UGT
    UDP-glucuronosyltransferase
    HPLC
    high-performance liquid chromatography
    TBST
    Tris-buffered saline Tween 20
    SI
    small intestine
    M1
    uncharacterized quercetin glucuronide.

  • Received January 25, 2011.
  • Accepted May 2, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 39 (8)
Drug Metabolism and Disposition
Vol. 39, Issue 8
1 Aug 2011
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Research ArticleArticle

Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

Bradley W. Bolling, Michael H. Court, Jeffrey B. Blumberg and C.-Y. Oliver Chen
Drug Metabolism and Disposition August 1, 2011, 39 (8) 1406-1414; DOI: https://doi.org/10.1124/dmd.111.038406

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Research ArticleArticle

Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

Bradley W. Bolling, Michael H. Court, Jeffrey B. Blumberg and C.-Y. Oliver Chen
Drug Metabolism and Disposition August 1, 2011, 39 (8) 1406-1414; DOI: https://doi.org/10.1124/dmd.111.038406
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