title: Alpha-tocopherol and ascorbic acid decrease the production of beta-apo-carotenals and increase the formation of retinoids from beta-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 beta-carotene. In the present study, we examined whether alpha-tocopherol, ascorbic acid, or the two combined can prevent smoke-altered beta-carotene metabolism. In vitro incubation of beta-carotene (10 micro mol/L) with lung postnuclear fractions from ferrets exposed to cigarette smoke was carried out in the absence or presence of alpha-tocopherol (50 micro mol/L), ascorbic acid (10 or 50 micro mol/L), or both vitamins to evaluate their effects on the production of beta-apo-carotenals and retinoids from beta-carotene. The oxidative cleavage metabolites of beta-carotene, beta-apo-carotenals (beta-apo-14', beta-apo-12', beta-apo-10', and beta-apo-8'), retinoic acid (RA), and retinal were analyzed by HPLC. We found that the smoke-enhanced production of individual beta-apo-carotenals was significantly decreased by 36-77% when alpha-tocopherol (50 micro mol/L) and ascorbic acid (50 micro mol/L) were added together to the incubation mixture. alpha-Tocopherol alone had a modest effect. Ascorbic acid in the presence of alpha-tocopherol inhibited the production of beta-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 ( approximately 3-fold, P < 0.05) when both alpha-tocopherol and ascorbic acid were added to the incubation mixtures. However, when ascorbic acid or alpha-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 alpha-tocopherol and ascorbic acid may act synergistically in preventing the enhanced oxidative excentric cleavage of beta-carotene induced by smoking exposure, thereby facilitating the conversion of beta-carotene into RA and retinal.
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Russell
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002338:Carotenoids / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D005289:Ferrets; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D012176:Retinoids / Q000096:biosynthesis*; D012907:Smoking / Q000009:adverse effects*; D024502:alpha-Tocopherol / Q000494:pharmacology*; D019207:beta Carotene / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D012176:Retinoids; D019207:beta Carotene; D002338:Carotenoids; D024502:alpha-Tocopherol; D001205:Ascorbic Acid