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 beta-carotene, alpha-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). beta-Carotene (1.5 microM) produced a prooxidant effect by promoting 12% isoprostane formation. Protein oxidation and DNA damage at 722 torr O(2) tension was not increased by beta-carotene; however, the antioxidant effect of beta-carotene was attenuated. The antioxidant effects of alpha-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 beta-carotene are dependent on O(2) tension and concentration of beta-carotene. Such findings may partially explain why selected populations, such as smokers, respond adversely when supplemented with beta-carotene.
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Nominally antioxidant molecules such as ascorbate have complex, multi-electron redox chemistry and can act as pro-oxidants, especially in the presence of free Fe or Cu.
“nominally antioxidant molecules such as ascorbate have complex, multi-electron redox chemistry, and can in fact act as pro-oxidants(502,503), especially in the presence of free Fe(208,213) or Cu(504).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [503]
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Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605023341802 · Cited by 3,638 · see citing works
Vitamin A metabolism in the human intestinal Caco-2 cell line
Quick, T. C., & Ong, D. E. (1990) · Biochemistry · doi:10.1021/bi00502a015 · Cited by 93 · see citing works
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Carotenoid radical chemistry and antioxidant/pro-oxidant properties
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The biology of ergothioneine, an antioxidant nutraceutical
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“in fact act as pro-oxidants(502,503), especially in the presence of free Fe(208,213) or Cu(504).”
BackgroundPinela, J., Prieto, M. A., Barreiro, M. F., Carvalho, A. M., Oliveira, M. B. P. P., Vázquez, J. A., & Ferreira, I. C. F. R. (2016) · Food and Bioproducts Processing · doi:10.1016/j.fbp.2016.02.002 · Cited by 44 · see citing works
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- Authors
- Zhang, P., & Omaye, S. T.
- Affiliations
- University of Nevada, Reno (US)
- Corresponding author
- Omaye, S.T
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 15
- Issue
- 1
- Pages
- 13-24
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2029143925
- Cited by
- 119
- References
- 2
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 12 · 2015: 2 · 2014: 2 · 2013: 9 · 2012: 4
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- beta-carotene, alpha-tocopherol, vitamin C, antioxidant activity, pro-oxidant activity, oxygen partial pressure, hypoxia, lipid peroxidation, protein oxidation, DNA damage, isoprostanes, carbonyl formation, p53, lung cells
- MeSH terms
- Antioxidants, Ascorbic Acid, DNA Damage, Free Radicals, Humans, Lung, Oxidation-Reduction, Oxygen, Proteins, Smoking, Vitamin E, Lipid Peroxidation, Reactive Oxygen Species, Oxidative Stress, Cell Culture Techniques, beta Carotene
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