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

Abstract

Previously, we found that exposing ferrets to cigarette smoke enhanced oxidative excentric cleavage of ␤-carotene. In the present study, we examined whether ␣-tocopherol, ascorbic acid, or the two combined can prevent smoke-altered ␤-carotene metabolism. In vitro incubation of ␤-carotene (10 mol/L) with lung postnuclear fractions from ferrets exposed to cigarette smoke was carried out in the absence or presence of ␣-tocopherol (50 mol/L), ascorbic acid (10 or 50 mol/L), or both vitamins to evaluate their effects on the production of ␤-apo-carotenals and retinoids from ␤-carotene. The oxidative cleavage metabolites of ␤-carotene, ␤-apo-carotenals (␤-apo-14Ј, ␤-apo-12Ј, ␤-apo-10Ј, and ␤-apo-8Ј), retinoic acid (RA), and retinal were analyzed by HPLC. We found that the smoke-enhanced production of individual ␤-apo-carotenals was significantly decreased by 36 -77% when ␣-tocopherol (50 mol/L) and ascorbic acid (50 mol/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 ␤-apo-carotenals in a dose-dependent manner, although ascorbic acid alone had no effect. In contrast, the production of RA and retinal among smokeexposed ferrets was substantially increased (ϳ3-fold, P Ͻ 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 Ͻ 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 ␤-carotene induced by smoking exposure, thereby facilitating the conversion of ␤-carotene into RA and retinal. J. Nutr. 134: 426 -430, 2004.

The effects of combined antioxidant (β‐carotene, α‐tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single‐strand breaks and levels of insulin‐like growth factor‐1/IGF‐binding protein 3 in the ferret model of lung cancer

“…22,28 This finding is in agreement with previous in vitro observations that the combination of AT and AA (but not AT or AA alone) can prevent smoke-enhanced oxidative cleavage of BC in the lung tissues of cigarette smoke-exposed ferrets. 26 Since smoke-exposure and NNK treatment did not decrease plasma AT concentration in the ferrets, with or without the AOX supplementation, and since vitamin C can regenerate both vitamin E and bcarotene from their respective radical cations, 40,41 the present Values are expressed as means 6 SEM (n 5 9-12).…”

“…The ferret is an excellent animal model for studying the protective effects of carotenoids on smoke-induced lung carcinogenesis because of the similarities between ferrets and humans in (i) the absorption 23,24 and metabolism of carotenoids [25][26][27] ; (ii) the production of cigarette smoke-induced lung premalignant lesions and (iii) the induction of lung tumors by the tobacco carcinogen (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)). 7,22,28,29 However, the effects of antioxidants on plasma antioxidant capacity and smoke-induced DNA damage have not been studied in the ferret model.…”

Lower Plasma Levels of Antioxidant Vitamins in Patients with Metabolic Syndrome: A Case Control Study

“…It is also known that a combination of these antioxidants may provide better antioxidant protection than a single antioxidant [44,45].…”

Antioxidants: Friend or foe for tuberculosis patients

“…α-TC radical is then recycled to α-TC by other antioxidants such as ascorbic acid (Vitamin C) and glutathione [7][8][9]. As soon as ascorbic acid recycles Vitamin E, it is transformed to the ascorbyl radical, which has a lower reactivity than α-TC radical [7].…”

“…As soon as ascorbic acid recycles Vitamin E, it is transformed to the ascorbyl radical, which has a lower reactivity than α-TC radical [7]. α-TC radical is also recycled to α-TC by β-carotene [9,10]. So, for proper antioxidant effect Vitamin E should be administered with another antioxidant and excess amount of vitamin E may be pro-oxidant per se.…”