Effects of β-Carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat

Abstract

The activities of several phase I and phase II xenobiotic-metabolizing enzymes have been measured in liver microsomes and cytosol of male rats that had been fed for 15 days with diets containing β-carotene or canthaxanthin (300 mg/kg diet) or an excess of vitamin A (70,000 IU/kg diet), or to which β-carotene had been administered by ip injections (7 × 10 mg/kg body weight). Microsomal cytochrome P-450 and the associated NADH- and NADPH-cytochrome c reductases were assayed, as well as several phase I and phase II enzyme activities. Phase I activities were markers of the families 1, 2, 3 and 4 of P-450; phase II activities were microsomal UDP glucuronosyl transferases (UGT) and cytosolic glutathione S-transferase (GST). Canthaxanthin accumulated in liver to a much higher level than did ingested or injected β-carotene. Canthaxanthin increased the liver content of cytochrome P-450 (control value x 1.7), and the activity of NADH-cytochrome c reductase (x 1.5), and of some P-450-dependent enzymes (ethoxy-, methoxy-, pentoxy- and benzoxyresorufin O-dealkylases; ×98, ×l5, ×6.5 and × 13, respectively), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate ω-hydroxylase). Phase II activities were also increased: UGT1 (×3.4), UGT2 (× 1.2) and GST (× 1.2). This induction profile, characterized by the very strong increase of the activity associated with P4501A1, and the co-induction of UGT1, closely resemble that of a classical inducer, 3-methylcholanthrene. By contrast, neither β-carotene (fed or injected), nor an excess of vitamin A induced any significant variation of the enzyme activities measured.