Antioxidant and prooxidant roles for β-carotene, α-tocopherol and ascorbic acid in human lung cells

Abstract

Experiments were conducted to determine the antioxidant and prooxidant effects of β-carotene, α-tocopherol and ascorbic acid on human lung cells at different oxygen (O 2) tensions. Free radical initiator, 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), was used to induce the cellular damage associated with lipid peroxidation, protein oxidation and DNA breaks. Under hypoxic conditions (0 torr O 2 tension) all compounds produced a concentration-dependent antioxidant effect. Mixtures of the three compounds exhibited greater protective affects than any individual compound. At 143 torr O 2 tension, all compounds exhibited concentration-dependent protective effects against AAPH-induced cellular lipid, protein and DNA damage. At 722 torr O 2 tension, cells exhibited a consistent increase in lipid peroxidation (isoprostane formation), protein oxidation (carbonyl formation) and DNA damage (p53 protein accumulation). β-Carotene (1.5 μ m) produced a prooxidant effect by promoting 12% isoprostane formation. Protein oxidation and DNA damage at 722 torr O 2 tension was not increased by β-carotene; however, the antioxidant effect of β-carotene was attenuated. The antioxidant effects of α-tocopherol, ascorbic acid, and mixtures of the three antioxidant compounds also were reduced by the high O 2 conditions. These results partially substantiate the hypothesis that the antioxidant and prooxidant effects of β-carotene are dependent on O 2 tension and concentration of β-carotene. Such findings may partially explain why selected populations, such as smokers, respond adversely when supplemented with β-carotene.