Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-C-14]quercetin-4' glucoside

W Mullen, B A Graf, S T Caldwell, R C Hartley, G G Duthie, C A Edwards, M E J Lean, A Crozier

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-C-14]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [C-14]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-C-14]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as C-14-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.

Original languageEnglish
Pages (from-to)6902-6909
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume50
Issue number23
DOIs
Publication statusPublished - 6 Nov 2002

Keywords

  • [2-C-14]quercetin-4'-glucoside
  • rat tissues
  • tandem mass spectrometry
  • methylated metabolites
  • glucuronides
  • sulfated derivatives
  • quercetin glucoronides
  • conjugated derivatives
  • dietary quercetin
  • heart-disease
  • glycosides
  • identification
  • bioavailability
  • accumulation
  • polyphenols
  • absorption

Cite this

Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-C-14]quercetin-4' glucoside. / Mullen, W ; Graf, B A ; Caldwell, S T ; Hartley, R C ; Duthie, G G; Edwards, C A ; Lean, M E J ; Crozier, A .

In: Journal of Agricultural and Food Chemistry, Vol. 50, No. 23, 06.11.2002, p. 6902-6909.

Research output: Contribution to journalArticle

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title = "Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-C-14]quercetin-4' glucoside",
abstract = "Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-C-14]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6{\%} of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [C-14]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-C-14]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2{\%} of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as C-14-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.",
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author = "W Mullen and Graf, {B A} and Caldwell, {S T} and Hartley, {R C} and Duthie, {G G} and Edwards, {C A} and Lean, {M E J} and A Crozier",
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T1 - Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-C-14]quercetin-4' glucoside

AU - Mullen, W

AU - Graf, B A

AU - Caldwell, S T

AU - Hartley, R C

AU - Duthie, G G

AU - Edwards, C A

AU - Lean, M E J

AU - Crozier, A

PY - 2002/11/6

Y1 - 2002/11/6

N2 - Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-C-14]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [C-14]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-C-14]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as C-14-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.

AB - Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-C-14]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [C-14]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-C-14]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as C-14-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.

KW - [2-C-14]quercetin-4'-glucoside

KW - rat tissues

KW - tandem mass spectrometry

KW - methylated metabolites

KW - glucuronides

KW - sulfated derivatives

KW - quercetin glucoronides

KW - conjugated derivatives

KW - dietary quercetin

KW - heart-disease

KW - glycosides

KW - identification

KW - bioavailability

KW - accumulation

KW - polyphenols

KW - absorption

U2 - 10.1021/jf020598p

DO - 10.1021/jf020598p

M3 - Article

VL - 50

SP - 6902

EP - 6909

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

SN - 0021-8561

IS - 23

ER -