PT  - JOURNAL ARTICLE
AU  - Erich Wolz
AU  - Hans Liechti
AU  - Brigitte Notter
AU  - Gottfried Oesterhelt
AU  - Andreas Kistler
TI  - Characterization of Metabolites of Astaxanthin in Primary Cultures of Rat Hepatocytes
DP  - 1999 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 456--462
VI  - 27
IP  - 4
4099  - http://dmd.aspetjournals.org/content/27/4/456.short
4100  - http://dmd.aspetjournals.org/content/27/4/456.full
SO  - Drug Metab Dispos1999 Apr 01; 27
AB  - The metabolism of the nonprovitamin A carotenoid astaxanthin was investigated in primary cultures of rat hepatocytes. In a time course study based on HPLC and gas chromatography-mass spectrometry analyses, one main metabolite, (rac)-3-hydroxy-4-oxo-β-ionone, was found. This metabolite was conjugated mainly into glucuronides, as demonstrated by glusulase treatment of the conjugates under sulfatase-inhibiting conditions. Within 24 h more than 50% astaxanthin was metabolized and conjugated. Deconjugation of the polar conjugates with glusulase and analyses with HPLC and gas chromatography-mass spectrometry identified two metabolites, (rac)-3-hydroxy-4-oxo-β-ionone and its reduced form (rac)-3-hydroxy-4-oxo-7,8-dihydro-β-ionone, indicating that the former was reduced in the conjugated form. We confirmed that the ketocarotenoid astaxanthin induces xenobiotic-metabolizing enzymes in rat liver in vivo. However, there were no differences in the metabolism of astaxanthin in cultured hepatocytes from rats that were pretreated with astaxanthin and, thus, with induced cytochrome P-450 systems compared with control hepatocytes. Neither liver microsomes from astaxanthin-pretreated nor control rats metabolized astaxanthin. These results indicated that the cytochrome P-450 enzymes were not involved in the metabolism of astaxanthin in rat hepatocytes. We conclude that astaxanthin was metabolized in primary cultures of rat hepatocytes into (rac)-3-hydroxy-4-oxo-β-ionone and its reduced form (rac)-3-hydroxy-4-oxo-7,8-dihydro-β-ionone independent of the xenobiotic-metabolizing enzymes induced by astaxanthin. The American Society for Pharmacology and Experimental Therapeutics