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

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Abstract
Previously, we found that exposing ferrets to cigarette smoke enhanced oxidative excentric cleavage of β-carotene. In the present study, we examined whether α-tocopherol, ascorbic acid, or the two combined can prevent smoke-altered β-carotene metabolism. In vitro incubation of β-carotene (10 μmol/L) with lung postnuclear fractions from ferrets exposed to cigarette smoke was carried out in the absence or presence of α-tocopherol (50 μmol/L), ascorbic acid (10 or 50 μmol/L), or both vitamins to evaluate their effects on the production of β-apo-carotenals and retinoids from β-carotene. The oxidative cleavage metabolites of β-carotene, β-apo-carotenals (β-apo-14′, β-apo-12′, β-apo-10′, and β-apo-8′), retinoic acid (RA), and retinal were analyzed by HPLC. We found that the smoke-enhanced production of individual β-apo-carotenals was significantly decreased by 36–77% when α-tocopherol (50 μmol/L) and ascorbic acid (50 μmol/L) were added together to the incubation mixture. α-Tocopherol alone had a modest effect. Ascorbic acid in the presence of α-tocopherol inhibited the production of β-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 α-tocopherol and ascorbic acid were added to the incubation mixtures. However, when ascorbic acid or α-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 α-tocopherol and ascorbic acid may act synergistically in preventing the enhanced oxidative excentric cleavage of β-carotene induced by smoking exposure, thereby facilitating the conversion of β-carotene into RA and retinal.

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