Vitamin A, Vitamin E, Lutein and β-Carotene in Lung Tissues from Subjects with Chronic Obstructive Pulmonary Disease and Emphysema

DOI: 10.4236/ojrd.2013.32008   PDF   HTML     3,500 Downloads   5,892 Views   Citations


Vitamin A (VA) and its active metabolites play an essential role in lung airway function. Patients with moderate to severe chronic obstructive pulmonary disease (COPD) have a lower serum retinol concentration, and improvement of their 1-second Forced Expiratory Volume (FEV1) is achieved with VA supplementation. In order to test our hypothesis that the VA signaling pathway is compromised in COPD, we obtained 20 lung samples from COPD patients differing in the degree of emphysema as judged by their FEV% values. All were smokers or were exposed to secondhand smoke. Levels of VA (retinol/retinyl ester), tocopherols and carotenoids (lutein, beta-carotene) in these samples were determined using HPLC. Additional analytes beside VA were included for their known roles as antioxidants and modulators of VA-action. VA levels (retinol/retinyl ester) decreased significantly with the increase in severity of emphysema. Among other analytes, α-tocopherol levels fell by 25.8% in the severe emphysema group in comparison to the mild emphysema group, and lutein levels similarly decreased in severe compared to moderate emphysema groups. However, beta-carotene levels remained unchanged. Thus there is a significant linear correlation between lung VA-levels and the severity of emphysema. There was also a significant reduction in the levels of α-, δ-tocopherol and lutein in the severe emphysema group of COPD patients who either smoked or were exposed to smoke.

Share and Cite:

Schäffer, M. , Roy, S. , Mukherjee, S. and Das, S. (2013) Vitamin A, Vitamin E, Lutein and β-Carotene in Lung Tissues from Subjects with Chronic Obstructive Pulmonary Disease and Emphysema. Open Journal of Respiratory Diseases, 3, 44-51. doi: 10.4236/ojrd.2013.32008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] G. Veigi, A. Scognamiglio, S. Baldacci, F. Pistelli and L. Carrozzi, “Epidemiology of Chronic Obstructive Pulmonary Disease (COPD),” Respiration, Vol. 68, No. 1, 2001, pp. 4-19. doi:10.1159/000050456
[2] C. Roth, “Factsheet Chronic Obstructive Pulmonary Disease (COPD),” National Institutes of Health, Vol. 10, 2010.
[3] S. K. Das, “Harmful Effects of Cigarette Smoking,” Molecular and Cellular Biochemistry, Vol. 253, No. 1, 2003, pp. 159-165. doi:10.1023/A:1026024829294
[4] S. A. Paiva, I. Godoy, H. Vannucchi, R. M. Favaro, R. R. Geraldo and A. O. Campana, “Assessment of Vitamin A status in Chronic Obstructive Pulmonary Disease Patients and Healthy Smokers,” American Journal of Clinical Nutrition, Vol. 64, No. 6, 1996, pp. 928-934.
[5] A. McDowell, A. Engle, J. T. Massey and K. R. Maurer, “Plan and Operation of the Second Health and Nutrition Examination Survey, 1976-80,” Vital and Health Statistics, Vol. 1, No. 15, 1981, pp. 81-1317.
[6] D. E. Ong and F. Chytil, “Changes in Levels of Cellular Retinol and Retinoic-Acid-Binding Proteins of Liver and Lung during Perinatal Development of Rat,” Proceedings of National Academy of Sciences USA, Vol. 73, No. 11, 1976, pp. 3976-3978. doi:10.1073/pnas.73.11.3976
[7] F. Chytil, “The Lungs and Vitamin A,” American Journal of Physiology, Vol. 261, No. 5, 1992, pp. L517-527.
[8] N. R. MacIntyre, “Chronic Obstructive Pulmonary Disease: Emerging Medical Therapies,” Respiratory Care, Vol. 49, No. 1, 2004, pp. 64-69.
[9] W. C. Bailey and D. P. Tashkin, “Pharmacologic Therapy: Novel Approaches for Chronic Obstructive Pulmonary Disease,” Annals of the American Thoracic Society, Vol. 4, No. 7, 2007, pp. 543-548. doi:10.1513/pats.200701-017FM
[10] F. S. Rosenthal, “Aerosol Probes of Emphysema Progression in Dogs Treated with All-Trans Retinoic Acid—An Exploratory,” Journal of Aerosol Medicine, Vol. 20, No. 2, 2007, pp. 83-96. doi:10.1089/jam.2007.0581
[11] G. D. Massaro and D. Massaro, “Retinoic Acid Treatment Abrogates Elastase-Induced Pulmonary Emphysema in Rats,” Nature Medicine, Vol. 3, No. 6, 1997, pp. 675-677. doi:10.1038/nm0697-675
[12] S. Mukherjee, T. Nayyar, F. Chytil and S. K. Das, “Mainstream and Sidestream Cigarette Smoke Exposure Increases Retinol in Guinea Pig Lungs,” Free Radical Biology and Medicine, Vol. 18, No. 3, 1995, pp. 507-514. doi:10.1016/0891-5849(94)00161-C
[13] H. J. Nelis, E. D’Haese and K. Vermis, “Vitamin E,” In: A. P. De Lenheer, W. E. Lambert and J. F. Van Bocxlaer, Eds., Modern Chromatographic Analysis of Vitamins, 3rd Edition, Marcel Dekker, New York, 2000, pp. 143-228.
[14] H. S. Falciglia, J. R. Johnson, J. Sullivan, et al., “Role of Antioxidant Nutrients and Lipid Peroxidation in Premature Infants with Respiratory Distress Syndrome and Bronchopulmonary Dysplasia,” American Journal of Perinatology, Vol. 20, No. 2, 2003, pp. 97-107. doi:10.1055/s-2003-38315
[15] F. M. Painter, “Lutein and Zeaxanthin,” Alternative Medicine Review, Vol. 10, No. 2, 2005, pp. 128-135.
[16] M. W. Schaffer, S. Sinha Roy, M. Mukherjee and S. K. Das, “Identification of Lutein, a Dietary Antioxidant Carotenoid in Guinea Pig Tissues,” Biochemical and Biophysical Research Communications, Vol. 374, No. 2, 2008, pp. 378-381. doi:10.1016/j.bbrc.2008.07.030
[17] M. W. Schaffer, S. S. Roy, S. Mukherjee, et al., “Qualitative and Quantitative Analysis of Retinol, Retinyl Esters, Tocopherols and Selected Carotenoids Out of Various Internal Organs from Different Species by HPLC,” Analytical Methods, Vol. 2, No. 9, 2010, pp. 1320-1332. doi:10.1039/c0ay00288g
[18] A. Matsumoto, H. Mizukami, S. Mizuno, et al., “Beta-Cryptoxanthin, a Novel Natural RAR Ligand, Induces ATP-Binding Cassette Transporters in Macrophages,” Biochemical Pharmacology, Vol. 74, No. 2, 2007, pp. 256-264. doi:10.1016/j.bcp.2007.04.014
[19] J. E Dowling and G. Wald, “The Biological Function of Vitamin A Acid,” Proceedings of the National Academy of Sciences USA, Vol. 46, No. 5, 1960, pp. 587-608. doi:10.1073/pnas.46.5.587
[20] R. Ziegler, S. Mayne and C. Swanson, “Nutrition and Lung Cancer,” Cancer Causes Control, Vol. 7, No. 1, 1996, pp. 157-177. doi:10.1007/BF00115646
[21] The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, “The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers,” New England Journal of Medicine, Vol. 330, No. 15, 1994, pp. 1029-1035. doi:10.1056/NEJM199404143301501
[22] G. S. Omenn, G. E. Goodman, M. D. Thornquist, et al., “Effects of a Combination of β-Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease,” New England Journal of Medicine, Vol. 334, 1996, pp. 1150-1155. doi:10.1056/NEJM199605023341802
[23] A. Morabia, A. Sorenson, S. K. Kumanyika and H. Abbey, “Vitamin A, Cigarette Smoking and Airway Obstruction,” American Review of Respiration Disease, Vol. 140, No. 5, 1989, pp. 1312-1316. doi:10.1164/ajrccm/140.5.1312
[24] A. Morabia, M. J. Menkes, G. W. Comstock and M. S. Tockman, “Serum Retinol and Airway Obstruction,” American Journal of Epidemiology, Vol. 132, No. 1, 1990, pp. 77-82.
[25] J. Lorenz and H. K Biesalski, “Vitamin A-Mangel und Bronchialkarzinom: Perspektiven der Chemoprevention bronchialer Tumoren,” Pneumologie, Vol. 47, No. 12, 1993, pp. 657-665.
[26] J. R. Mata, N. L. Mata and A. T. C. Tsin, “Substrate Specificity of Retinyl Ester Hydrolase Activity in Retinal Pigment Epithelium,” Journal of Lipid Research, Vol. 39, 1998, pp. 604-612.
[27] T. E. Edes, S. M. Kwan, C. S. Buckley and W. H. Thornton, “Tissue Vitamin A Repletion Is Impaired by Exposure to Carcinogen,” International Journal of Cancer, Vol. 50, No. 1, 1992, pp. 99-102. doi:10.1002/ijc.2910500120
[28] T. E. Edes and D. S. Gysbers, “Carcinogen-Induced Tissue Vitamin A Depletion. Potential Protective Advantages of β-Carotene,” Annals of the New York Academy of Sciences, Vol. 686, 1993, pp. 203-212. doi:10.1111/j.1749-6632.1993.tb39176.x
[29] R. Kawaguchi, J. Yu, J. Honda, et al., “A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A,” Science, Vol. 315, No. 5831, 2007, pp. 820-825. doi:10.1126/science.1136244
[30] H. K. Biesalski, R. Reifen, F. Pürst and M. Edris, “Retinyl Palmitate Supplementation by Inhalation of an Aerosol Improves Vitamin A Status of Preschool Children in Gondar (Ethiopia),” British Journal of Nutrition, Vol. 82, No. 3, 1999, pp. 179-182.
[31] M. Kohlhaufl, K. Haussinger, F. Stanzel, et al., “Inhalation of Aerosolized Vitamin A: Reversibility of Metaplasia and Dysplasia of Human Respiratory Epithelia a Prospective Pilot Study,” European Journal of Medical Research, Vol. 7, No. 2, 2002, pp. 72-78.
[32] M. Frankenberger, I. Heimbeck, W. Moller, et al., “Inhaled All-Trans Retinoic Acid in an Individual with Severe Emphysema,” European Respiratory Journal, Vol. 34, No. 6, 2009, pp. 1487-1489. doi:10.1183/09031936.00105309
[33] S. Van Eijl, E. Mortaz, C. Versluis, F. P. Nijkamp, G. Folkerts and N. Bloksma, “A Low Vitamin A Status Increases the Susceptibility to Cigarette Smoke-Induced Lung Emphysema in C57BL/6J Mice,” Journal of Physiology and Pharmacology, Vol. 62, No. 2, 2011, pp. 175-182.
[34] S. Mahabir, K. Schendel, Y. Q. Dong, S. L. Barrera, M. R. Spitz and M. R. Forman, “Dietary α-, β-, γ-and δ-Tocopherols in Lung Cancer Risk,” International Journal of Cancer, Vol. 123, No. 5, 2008, pp. 1173-1180. doi:10.1002/ijc.23649
[35] J. L. Napoli, A. M. McCormick, B. O’Meara and E. A. Dratz, “Vitamin A Metabolism: Alpha-Tocopherol Modulates Tissue Retinol Levels in Vivo, and Retinyl Palmitate Hydrolysis in Vitro,” Archives of Biochemistry and Biophysics, Vol. 230, No. 1, 1984, pp. 194-202. doi:10.1016/0003-9861(84)90100-0
[36] J. M. Zingg, “Modulation of Signal Transduction by Vitamin E,” Molecular Aspects of Medicine, Vol. 28, No. 5-6, 2007, pp. 481-506. doi:10.1016/j.mam.2006.12.009
[37] E. Reiter, Q. Jiang and S. Christen, “Anti-Inflammatory Properties of α-and γ-Tocopherol,” Molecular Aspects of Medicine, Vol. 28, No. 5-6, 2007, pp. 668-691. doi:10.1016/j.mam.2007.01.003
[38] Q. Jiang, I. Elson-Schwab, C. Courtemanche and B. N. Ames, “Gamma-Tocopherol and Its Major Metabolite, in Contrast to Alpha-Tocopherol, Inhibit Cyclooxygenase Activity in Macrophages and Epithelial Cells,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 21, 2000, pp. 11494-11499. doi:10.1073/pnas.200357097
[39] J. Roca-Ferrer, L. Pujols, C. Agusti, et al.., “Cyclooxigenase-2 Levels Are Increased in the Lung Tissue and Bronchial Tumors of Patients with Chronic Obstructive Pulmonary Disease,” Archivos de Bronconeumología, Vol. 47, No. 12, 2011, pp. 584-589. doi:10.1016/j.arbres.2011.05.015
[40] C. M. Greene, D. Waters, R. M. Clark, J. H. Contois and M. L. Fernandez, “Plasma LDL and HDL Characteristics and Carotenoid Content Are Positively Influenced by Egg Consumption in an Elderly Population,” Nutrition & Metabolism, Vol. 3, No. 6, 2006, pp. 6-14. doi:10.1186/1743-7075-3-6
[41] B. Li, P. Vachali, J. M. Frederick and P. S. Bernstein, “Identification of StARD3 as a Lutein-Binding Protein in the Macula of the Primate Retina,” Biochemistry, Vol. 50, No. 13, 2011, pp. 2541-2549. doi:10.1021/bi101906y
[42] H. Watari, F. Arakane, C. Moog-Lutz, et al.., “MLN64 Contains a Domain with Homology to the Steroidogenic Acute Regulatory Protein (StAR) that Stimulates Steroidogenesis,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 16, 1997, pp. 8462-8467.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.