Determination of Flavonol Metabolites in Plasma and Tissues of Rats by HPLC−Radiocounting and Tandem Mass Spectrometry Following Oral Ingestion of [2-¹⁴C]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-(14)C]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. [(14)C]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-(14)C]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 (14)C-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.

Natural polyphenol disposition via coupled metabolic pathways

“…Even though scientific researches have emphasized on studying parent polyphenols, recent studies indicate that some polyphenol metabolites may accumulate in certain target tissues rather than just equilibrate between blood and plasma [116][117][118][119]. Whether these are active metabolites, have not been carefully studies and need more of our attention since they are present at much higher concentration in vivo.…”

Urinary Metabolite Profiling Reveals CYP1A2-Mediated Metabolism of NSC686288 (Aminoflavone)

“…Structures of major AF metabolites were elucidated through analyzing the fragmentation pattern recorded by tandem mass spectrometry. Like typical flavone compounds, the rDA reaction contributes to the formation of major daughter ions of AF and its metabolites by breaking the C-ring (Mullen et al, 2002). Examining the product ions from the rDA reaction and the breaking of the C-C bond between the B-and C-rings can pinpoint whether the phase I reaction happens on the A-, B-, or C-rings.…”

Absorption and Metabolization of Cytoprotective Epicatechin Thio Conjugates in Rats

“…Phenolic metabolites from plasma were precipitated and extracted as described in the literature (Mullen et al, 2002). In brief, 1 ml of plasma was acidified with 5% HCl and then acetonitrile (2.5 ml) was added, and the sample was vortexed for 30 s every 2 min over 10 min.…”