Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

Bradley W Bolling; Michael H Court; Jeffrey B Blumberg; C-Y Oliver Chen

doi:10.1124/dmd.111.038406

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Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

Journal article

Open access

Peer reviewed

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, Vol.39(8), pp.1406-1414

08/2011

DOI: https://doi.org/10.1124/dmd.111.038406

Handle:

https://hdl.handle.net/2376/112674

PMCID: PMC3141883

PMID: 21543555

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Abstract

Microsomes - metabolism

Intestinal Mucosa - metabolism

Enterocytes - metabolism

Rats, Inbred F344

Rats

Male

Microsomes - enzymology

Chromatography, High Pressure Liquid

Blotting, Western

Intestine, Small - enzymology

Dose-Response Relationship, Drug

Animals

Glucuronides - metabolism

Quercetin - pharmacokinetics

Glucuronosyltransferase - metabolism

Intestinal Mucosa - enzymology

Intestine, Small - metabolism

Enterocytes - enzymology

Quercetin - metabolism

Aging - metabolism

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.

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Title: Microsomal quercetin glucuronidation in rat small intestine depends on age and segment
Creators: Bradley W Bolling - Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
Michael H Court
Jeffrey B Blumberg
C-Y Oliver Chen
Publication Details: Drug metabolism and disposition, Vol.39(8), pp.1406-1414
Academic Unit: Veterinary Clinical Sciences, Department of
Publisher: United States
Grant note: K12-GM074869 / NIGMS NIH HHS K12 GM074869 / NIGMS NIH HHS R01-GM061834 / NIGMS NIH HHS R01 GM061834 / NIGMS NIH HHS
Identifiers: 99900547746401842
Language: English
Resource Type: Journal article