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Nutrient Interactions and Toxicity

-Tocopherol and Ascorbic Acid Decrease the Production of ß-Apo-carotenals and Increase the Formation of Retinoids from ß-Carotene in the Lung Tissues of Cigarette Smoke–Exposed Ferrets In Vitro¹

Nutrition and Cancer Biology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

²To whom correspondence should be addressed. E-mail: xiang-dong.wang{at}Tufts.edu.

Previously, we found that exposing ferrets to cigarette smoke enhanced oxidative excentric cleavage of ß-carotene. In the present study, we examined whether -tocopherol, ascorbic acid, or the two combined can prevent smoke-altered ß-carotene metabolism. In vitro incubation of ß-carotene (10 µmol/L) with lung postnuclear fractions from ferrets exposed to cigarette smoke was carried out in the absence or presence of -tocopherol (50 µmol/L), ascorbic acid (10 or 50 µmol/L), or both vitamins to evaluate their effects on the production of ß-apo-carotenals and retinoids from ß-carotene. The oxidative cleavage metabolites of ß-carotene, ß-apo-carotenals (ß-apo-14', ß-apo-12', ß-apo-10', and ß-apo-8'), retinoic acid (RA), and retinal were analyzed by HPLC. We found that the smoke-enhanced production of individual ß-apo-carotenals was significantly decreased by 36–77% when -tocopherol (50 µmol/L) and ascorbic acid (50 µmol/L) were added together to the incubation mixture. -Tocopherol alone had a modest effect. Ascorbic acid in the presence of -tocopherol inhibited the production of ß-apo-carotenals in a dose-dependent manner, although ascorbic acid alone had no effect. In contrast, the production of RA and retinal among smoke-exposed ferrets was substantially increased (3-fold, P < 0.05) when both -tocopherol and ascorbic acid were added to the incubation mixtures. However, when ascorbic acid or -tocopherol alone was added, the production of RA among smoke-exposed ferrets increased only modestly (80%, P < 0.05) and did not differ from the RA levels in control ferrets. In conclusion, these data indicate that -tocopherol and ascorbic acid may act synergistically in preventing the enhanced oxidative excentric cleavage of ß-carotene induced by smoking exposure, thereby facilitating the conversion of ß-carotene into RA and retinal.

KEY WORDS: • carotenoids • retinoids • -tocopherol • ascorbic acid • cigarette smoke

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