Effects of beta-carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat

Food Chem Toxicol. 1994 Aug;32(8):735-42. doi: 10.1016/s0278-6915(09)80006-9.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Canthaxanthin / analysis
  • Canthaxanthin / pharmacology*
  • Carotenoids / analysis
  • Carotenoids / pharmacology*
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction / drug effects
  • Glucuronosyltransferase / biosynthesis
  • Glutathione Transferase / biosynthesis
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • NADH Dehydrogenase / biosynthesis
  • Rats
  • Rats, Wistar
  • Vitamin A / analysis
  • Xenobiotics / metabolism*
  • beta Carotene

Substances

  • Xenobiotics
  • beta Carotene
  • Vitamin A
  • Carotenoids
  • Canthaxanthin
  • Cytochrome P-450 Enzyme System
  • NADH Dehydrogenase
  • Glucuronosyltransferase
  • Glutathione Transferase