Characterization of metabolites of astaxanthin in primary cultures of rat hepatocytes

The metabolism of the nonprovitamin A carotenoid astaxanthin was investigat ed 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-beta-ionone, was found. This metabolite was conjuga ted 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 co njugates with glusulase and analyses with HPLC and gas chromatography-mass spectrometry identified two metabolites, (rac)-3-hydroxy-4-oxo-beta-ionone and its reduced form (rac)-3-hydroxy-4-oxo-7,8-dihydro-beta-ionone, indicat ing that the former was reduced in the conjugated form. We confirmed that t he ketocarotenoid astaxanthin induces xenobiotic-metabolizing enzymes in ra t liver in vivo. However, there were no differences in the metabolism of as taxanthin in cultured hepatocytes from rats that were pretreated with astax anthin and, thus, with induced cytochrome P-450 systems compared with contr ol hepatocytes, Neither liver microsomes from astaxanthin-pretreated nor co ntrol rats metabolized astaxanthin, These results indicated that the cytoch rome P-450 enzymes were not involved in the metabolism of astaxanthin in ra t hepatocytes, We conclude that astaxanthin was metabolized in primary cult ures of rat hepatocytes into (rac)-3-hydroxy-4-oxo-beta-ionone and its redu ced form (rac)-3-hydroxy-4oxo-7,8-dihydro-beta-ionone independent of the xe nobiotic-metabolizing enzymes induced by astaxanthin.