EFFECTS OF BETA-CAROTENE AND CANTHAXANTHIN ON LIVER XENOBIOTIC-METABOLIZING ENZYMES IN THE RAT

The activities of several phase I and phase II xenobiotic-metabolizing enzymes have been measured in liver microsomes and cytosol of male ra ts that had been fed for 15 days with diets containing beta-carotene o r canthaxanthin (300 mg/kg diet) or an excess of vitamin A (70,000 IU/ kg diet), or to which beta-carotene had been administered by ip inject ions (7 x 10 mg/kg body weight). Microsomal cytochrome P-450 and the a ssociated NADH- and NADPH-cytochrome c reductases were assayed, as wel l as several phase I and phase II enzyme activities. Phase I activitie s were markers of the families 1, 2, 3 and 4 of P-450; phase II activi ties were microsomal UDP glucuronosyl transferases (UGT) and cytosolic glutathione S-transferase (GST). Canthaxanthin accumulated in liver t o a much higher level than did ingested or injected beta-carotene. Can thaxanthin increased the liver content of cytochrome P-450 (control va lue x 1.7), and the activity of NADH-cytochrome c reductase (x 1.5), a nd of some P-450-dependent enzymes (ethoxy-, methoxy-, pentoxy- and be nzoxyresorufin O-dealkylases; x 98, x 15, x 6.5 and x 13, respectively ), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate omega-hydroxylase). Phase II activities wer e also increased: UGT1 (x 3.4), UGT2 (x 1.2) and GST (x 1.2). This ind uction profile, characterized by the very strong increase of the activ ity associated with P4501A1, and the co-induction of UGT1, closely res emble that of a classical inducer, 3-methylcholanthrene. By contrast, neither beta-carotene (fed or injected), nor an excess of vitamin A in duced any significant variation of the enzyme activities measured.