Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of beta-carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat. 807 Jul 38

To determine whether carotenoids can modulate xenobiotic-metabolizing enzymes in mice, catalytic activities of several phase I and phase II enzymes have been measured in liver microsomes and cytosol of male Swiss mice fed diets containing beta-carotene, beta-apo-8'-carotenal, canthaxanthin, or astaxanthin (300 mg/kg diet) or treated with 3-methylcholanthrene (3-MC) (3 times at 50 mg/kg ip) for 15 days. Canthaxanthin increased CYP 1A-dependent activities: ethoxyresorufin O-deethylase (EROD) was increased 3-fold, pentoxyresorufin dealkylase (PROD) was increased 2.5-fold, and methoxyresorufin O-demethylase (MROD) was increased 1.6-fold; these increases were much less than those induced by 3-MC, which induced EROD 49-fold, PROD 10-fold, and MROD 4-fold. 3-MC, but not canthaxanthin, also increased relative liver weight, liver P-450 content, NADH-cytochrome c reductase, and benzoxyresorufin dearylase. The three other carotenoids had little or no effect on phase I enzymes. Among the phase II enzyme activities, only NADPH-quinone reductase was slightly increased by 3-MC and carotenoids, except beta-carotene. Among the three carotenoids that have previously been found to be powerful CYP 1A inducers in the rat, i.e., canthaxanthin, astaxanthin, and beta-apo-8'-carotenal, only canthaxanthin shows some (weak) inducing effect of CYP 1A in the 3-MC-responsive Swiss mice, indicating that the mechanism of CYP 1A induction by carotenoids may not be the same as that by 3-MC. In addition, the fact that beta-carotene has no effect on the tested enzymes does not support the hypothesis that the modulation of xenobiotic metabolism is a possible mechanism for the antimutagenic and anticarcinogenic effects of beta-carotene, which have been demonstrated in several in vivo models in mice.
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PMID:Effects of provitamin A or non-provitamin A carotenoids on liver xenobiotic-metabolizing enzymes in mice. 910 53