Abstract1. The current study demonstrated that there is still new information to be obtained on the chemical and biological transformation of the widely studied flavonoid quercetin.2. In rat hepatocytes thirty five metabolites of quercetin were observed by using high resolution mass spectrometry. The metabolites included glucuronides, sulphates, mixed sulphate/glucuronide metabolites and methylated versions of these metabolites.3. Several metabolites were formed from chemical degradation products of quercetin which were found to form in Krebs-Henseleit (KH) buffer, degradants of quercetin were also formed in the buffer under the conditions used for hepatocyte incubations.4. The degradants and metabolites of quercetin were characterised by using high resolution MS 2 . It was observed that the glutathione (GSH) conjugates of quercetin formed in large amounts in ammonium bicarbonate solution although the pattern of conjugates formed was different from that observed in hepatocytes suggesting some degree on enzymatic control on GSH conjugate formation in the hepatocyte incubations.5. GSH conjugates were not formed when GSH was included in incubations of quercetin in KH buffer alone and only small amounts of quercetin degradation occurred. Instead GSH was extensively converted into GSSG thus presumably reducing the levels of oxygen in the incubation thus preventing quercetin degradation.
1. The metabolism of ferulic acid (FA) has been studied in a number of different systems and several metabolites of FA have been characterised. No previous work has been carried out using hepatocytes to characterise the metabolism of FA. 2. A metabolomics approach in combination with high resolution mass spectrometry was used to characterise the metabolites of FA formed in isolated rat hepatocytes. FA was incubated with rat hepatocytes and the metabolites formed were profiled at 30 and 120 minutes. The metabolites were characterised according to their accurate mass at <2 ppm using Fourier transform mass spectrometry (FT-MS). 3. Sixteen metabolites of FA were identified. The most abundant metabolite was the sulphate of FA and this was followed by FA glucuronide and glycine conjugates. A wide range of low level metabolites were produced in the hepatocyte incubations. Novel metabolites resulted from side chain oxidation. 4. In addition, a glutathione (GSH) adduct of FA was formed. Incubation of a solution of FA with GSH also resulted in formation of this adduct indicating that it could be formed purely by a chemical reaction. Thus the metabolism of FA in rat hepatocytes is more complex than previously described.
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