Effects of provitamin a or non‐provitamin a carotenoids on liver xenobiotic‐metabolizing enzymes in mice

Publisher Website
Google Scholar
Abstract
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 P‐carotene, β‐apo‐8'‐carotenal, canthaxanthin, or astaxanthin (300 mg/kg diet) or treated with 3‐methyl‐cholanthrene (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 1 enzymes. Among the phase 11 enzyme activities, only NADPH‐quinone reductase was slightly increased by 3‐MC and carotenoids, except P‐carotene. Among the three carotenoids that have previously been found to be powerful CYP 1A inducers in the rat, i.e., canthaxanthin, astaxanthin, and β‐apo‐8'‐carotenal, only canthaxanthin shows some (weak) inducing effect of CYP IA 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 P‐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 β‐carotene, which have been demonstrated in several in vivo models in mice.