Metabolic fate of [14C] quercetin in the ACI rat.

To explain why quercetin, a mutagenic flavonoid distributed widely in edible plants, showed no carcinogenicity in experimental animals, overall metabolic fate of the drug was pursued using radiolabeled compound. [4-(14)C]Quercetin was administered orally or intraperitoneally to male ACI rats and its distribution, metabolism and excretion were studied by autoradiography and/or quantitation of radioactivity, and chemical analysis. [14C]Quercetin was also administered intravenously, intraperitoneally or orally to bile duct-cannulated rats and radioactivities in CO2 expired, bile, urine and feces were measured. To elucidate chemical structure of radiolabeled flavonoids in the bile and urine, urinary flavonoids derived from the rats given non-labeled quercetin diet was analyzed chemically. When [14C]-quercetin was administered orally, around 20% of the administered [14C]quercetin was absorbed from the digestive tract, more than 30% was decomposed to yield 14CO2 and around 30% was excreted unchanged in the feces. The absorbed [14C]quercetin was rapidly excreted into the bile and urine within 48 hours as the glucuronide and sulfate conjugates of [14C]quercetin, 3'-O-monomethyl [14C]quercetin and 4'-O-monomethyl [14C]quercetin. The present data indicate that the lack of carcinogenicity of quercetin in the rat is attributable to neither its poor absorption from the digestive tract nor its microbial degradation in the tract. Efficient metabolism and elimination of quercetin may be one reason of the lack of carcinogenicity.