Absorption, Disposition, Metabolism, and Excretion of [3-¹⁴C]Caffeic Acid in Rats

Abstract

Male Sprague-Dawley rats ingested 140 × 10(6) dpm of [3-(14)C]trans-caffeic acid, and over the ensuing 72 h period, body tissues, plasma, urine, and feces were collected and the overall levels of radioactivity determined. Where sufficient radioactivity had accumulated, samples were analyzed by HPLC with online radioactivity and tandem mass spectrometric detection. Nine labeled compounds were identified, the substrate and its cis isomer, 3'-O- and 4'-O-sulfates and glucuronides of caffeic acid, 4'-O-sulfates and glucuronides of ferulic acid, and isoferulic acid-4'-O-sulfate. Four unidentified metabolites were also detected. After passing down the gastrointestinal tract, the majority of the radiolabeled metabolites were excreted in urine with minimal accumulation in plasma. Only relatively small amounts of an unidentified (14)C-labeled metabolite were expelled in feces. There was little or no accumulation of radioactivity in body tissues, including the brain. The overall recovery of radioactivity 72 h after ingestion of [3-(14)C]caffeic acid was ∼80% of intake.

Bioavailability of tomato polyphenols is enhanced by processing and fat addition: Evidence from a randomized feeding trial

“…All free forms underwent an extensive metabolism to their glucuronide and sulfate forms if the concentration of the aglycone was compared with the resulting metabolites. The compounds with the highest excretion were FA metabolites, probably due to the metabolism of 5‐CQA and CA . Significant differences were obtained in FA between tomato and OF, but their metabolites showed similar excretion among the three interventions.…”

Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium

“…The latter two compounds also have iron-chelating activity. The Nox1 inhibitors tested were selected based on their bioavailability in animals [15], [16], [17], [18], [19], [20]. The best small molecule inhibitors identified will be used as scaffolds for further modification to be developed into more specific Nox1 inhibitors.…”

The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites

“…After oral ingestion, enteral metabolism of methyl esters of p ‐coumaric, caffeic and ferulic acids (compounds 5 , 6 , and 7 , respectively; Figure ) involves de‐esterification and primarily sulfate or, to a lesser extent, glucuronide conjugation, leading to the formation of compounds 5a ‐ 5d , 6a ‐ 6g , and 7a ‐ 7c , respectively (Figure A) . In case of the catechol methyl caffeate ( 6 ) and its metabolite caffeic acid ( 6a ), methylation by catechol‐ O ‐methyltransferase (COMT) also takes place, with subsequent formation of the sulfate conjugates of ferulic acid ( 6b ) and isoferulic acid ( 6d ) as main products . Following absorption, glucuronidation, methylation and/or sulfation takes place in the liver and the formed metabolites participate in enterohepatic circulation.…”

“…95 In case of the catechol methyl caffeate (6) and its metabolite caffeic acid (6a), methylation by catechol-O-methyltransferase (COMT) also takes place, with subsequent formation of the sulfate conjugates of ferulic acid (6b) and isoferulic acid (6d) as main products. [94][95][96] Following absorption, glucuronidation, methylation and/or sulfation takes place in the liver and the formed metabolites participate in enterohepatic circulation. Methylation by COMT was also observed in the kidneys.…”