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 rats that had been fed for 15 days with diets containing beta-carotene or 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 injections (7 x 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 beta-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; x98, x15, x6.5 and x13, respectively), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate omega-hydroxylase). Phase II activities were also increased: UGT1 (x3.4), UGT2 (x1.2) and GST (x1.2). 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 beta-carotene (fed or injected), nor an excess of vitamin A induced any significant variation of the enzyme activities measured.
Astorg
P
P
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.
Gradelet
S
S
Leclerc
J
J
Canivenc
M C
MC
Siess
M H
MH
D000818:Animals; D016644:Canthaxanthin / Q000032:analysis / Q000494:pharmacology*; D002338:Carotenoids / Q000032:analysis / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009245:NADH Dehydrogenase / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000032:analysis; D015262:Xenobiotics / Q000378:metabolism*; D019207:beta Carotene
D015262:Xenobiotics; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D016644:Canthaxanthin; D003577:Cytochrome P-450 Enzyme System; D009245:NADH Dehydrogenase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase