Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

Matthew A Tucker, Brandon M Fox, Nichole Seigler, Paula Rodriquez-Miguelez, Jacob Looney, Jeffrey Thomas, Kathleen T McKie, Caralee Forseen, Gareth Davison

Research output: Contribution to journalArticle

Abstract

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3%), compared to no change following placebo (Δ - 0.8 ± 1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 μM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 μM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

LanguageEnglish
Number of pages1
JournalOxidative Medicine and Cellular Longevity
Volume2019
DOIs
Publication statusPublished - 19 Jun 2019

Fingerprint

Oxidative stress
Cystic Fibrosis
Oxidative Stress
Antioxidants
Blood Vessels
Placebos
Dilatation
Eating
Paraoxon
Thioctic Acid
Doppler Ultrasonography
Brachial Artery
Lipid Peroxides
alpha-Tocopherol
Vitamin E
Biological Availability
Ascorbic Acid
Nitric Oxide
Ultrasonics
Serum

Cite this

Tucker, Matthew A ; Fox, Brandon M ; Seigler, Nichole ; Rodriquez-Miguelez, Paula ; Looney, Jacob ; Thomas, Jeffrey ; McKie, Kathleen T ; Forseen, Caralee ; Davison, Gareth. / Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress. In: Oxidative Medicine and Cellular Longevity. 2019 ; Vol. 2019.
@article{06a5e39ae49d401e81a3fc740f1d2dfe,
title = "Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress",
abstract = "Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3{\%}), compared to no change following placebo (Δ - 0.8 ± 1.9{\%}). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 μM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 μM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.",
author = "Tucker, {Matthew A} and Fox, {Brandon M} and Nichole Seigler and Paula Rodriquez-Miguelez and Jacob Looney and Jeffrey Thomas and McKie, {Kathleen T} and Caralee Forseen and Gareth Davison",
note = "[1] A. Cantin, “Cystic fibrosis lung inflammation: early, sustained, and severe,” American journal of Respiratory and Critical Care Medicine, vol. 151, no. 4, pp. 939–941, 1995. [2] M. Gruet, T. Troosters, and S. Verges, “Peripheral muscle abnormalities in cystic fibrosis: etiology, clinical implications and response to therapeutic interventions,” Journal of Cystic Fibrosis, vol. 16, no. 5, pp. 538–552, 2017. [3] B. J. Plant, C. H. Goss, W. D. Plant, and S. C. Bell, “Management of comorbidities in older patients with cystic fibrosis,” The Lancet Respiratory Medicine, vol. 1, no. 2, pp. 164–174, 2013. [4] D. S. Celermajer, K. E. Sorensen, V. M. Gooch et al., “Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis,” The Lancet, vol. 340, no. 8828, pp. 1111–1115, 1992. [5] T. Gori, S. Muxel, A. Damaske et al., “Endothelial function assessment: flow-mediated dilation and constriction provide different and complementary information on the presence of coronary artery disease,” European Heart Journal, vol. 33, no. 3, pp. 363–371, 2012. [6] A. Uehata, E. H. Lieberman, M. D. Gerhard et al., “Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery,” Vascular Medicine, vol. 2, no. 2, pp. 87–92, 1997. [7] D. Green, “Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function,” Journal of Applied Physiology, vol. 99, no. 3, pp. 1233-1234, 2005. [8] S. Poore, B. Berry, D. Eidson, K. T. McKie, and R. A. Harris, “Evidence of vascular endothelial dysfunction in young patients with cystic fibrosis,” Chest Journal, vol. 143, no. 4, pp. 939–945, 2013. [9] P. Rodriguez-Miguelez, J. Thomas, N. Seigler et al., “Evidence of microvascular dysfunction in patients with cystic fibrosis,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 310, no. 11, pp. H1479–H1485, 2016. [10] R. K. Brown and F. J. Kelly, “Role of free radicals in the pathogenesis of cystic fibrosis,” Thorax, vol. 49, no. 8, pp. 738– 742, 1994. [11] R. K. Brown, H. Wyatt, J. F. Price, and F. J. Kelly, “Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress,” European Respiratory Journal, vol. 9, no. 2, pp. 334– 339, 1996. [12] A. L. Coates, P. Boyce, D. Muller, M. Mearns, and S. Godfrey, “The role of nutritional status, airway obstruction, hypoxia, and abnormalities in serum lipid composition in limiting exercise tolerance in children with cystic fibrosis,” Acta Paediatrica, vol. 69, no. 3, pp. 353–358, 1980. [13] A. Lezo, F. Biasi, P. Massarenti et al., “Oxidative stress in stable cystic fibrosis patients: do we need higher antioxidant plasma levels?,” Journal of Cystic Fibrosis, vol. 12, no. 1, pp. 35–41, 2013. [14] P. Montuschi, P. Paredi, M. Corradi et al., “8-Isoprostane, a biomarker of oxidative stress, is increased in cystic fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 3, 1999. [15] A. Van Der Vliet, J. P. Eiserich, G. P. Marelich, B. Halliwell, and C. E. Cross, “Oxidative stress in cystic fibrosis: does it occur and does it matter?,” Advances in Pharmacology, vol. 38, pp. 491–513, 1996. [16] L. G. Wood, D. A. Fitzgerald, P. G. Gibson, D. M. Cooper, C. E. Collins, and M. L. Garg, “Oxidative stress in cystic fibrosis: dietary and metabolic factors,” Journal of the American College of Nutrition, vol. 20, no. 2, pp. 157–165, 2001. [17] G. Zalba, G. S. Jos{\'e}, M..́ U. Moreno et al., “Oxidative stress in arterial hypertension: role of NAD(P)H oxidase,” Hypertension, vol. 38, no. 6, pp. 1395–1399, 2001. [18] F. Galli, A. Battistoni, R. Gambari et al., “Oxidative stress and antioxidant therapy in cystic fibrosis,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1822, no. 5, pp. 690–713, 2012. [19] R. A. Harris, S. K. Nishiyama, D. W. Wray, V. Tedjasaputra, D. M. Bailey, and R. S. Richardson, “The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia,” European Journal of Applied Physiology, vol. 107, no. 4, pp. 445–453, 2009. [20] S. J. Ives, R. A. Harris, M. A. H. Witman et al., “Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox balance,” Hypertension, vol. 63, no. 3, pp. 459–467, 2014. [21] C. S{\'a}nchez-Moreno, M. P. Cano, B. de Ancos et al., “Consumption of high-pressurized vegetable soup increases plasma vitamin C and decreases oxidative stress and inflammatory biomarkers in healthy humans,” The Journal of Nutrition, vol. 134, no. 11, pp. 3021–3025, 2004. [22] D. W. Wray, S. K. Nishiyama, R. A. Harris et al., “Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption,” Hypertension, vol. 59, no. 4, pp. 818–824, 2012. [23] G. K. Kapuku, F. A. Treiber, H. C. Davis, G. A. Harshfield, B. B. Cook, and G. A. Mensah, “Hemodynamic function at rest, during acute stress, and in the field: predictors of cardiac structure and function 2 years later in youth,” Hypertension, vol. 34, no. 5, pp. 1026–1031, 1999. [24] S. P. Wolff, “[18] Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides,” Methods in Enzymology, vol. 233, pp. 182–189, 1994. [25] P. Medlow, J. McEneny, M. H. Murphy, T. Trinick, E. Duly, and G. W. Davison, “Exercise training protects the LDL I subfraction from oxidation susceptibility in an aged human population,” Atherosclerosis, vol. 239, no. 2, pp. 516–522, 2015. [26] D. L. Kellogg Jr, P. E. P{\'e}rgola, K. L. Piest et al., “Cutaneous active vasodilation in humans is mediated by cholinergic nerve cotransmission,” Circulation Research, vol. 77, no. 6, pp. 1222– 1228, 1995. [27] A. T. Society, “Standardization of Spirometry, 1994 Update. American Thoracic Society,” American Journal of Respiratory and Critical Care Medicine, vol. 152, no. 3, pp. 1107–1136, 1995. [28] P. H. Quanjer, S. Stanojevic, T. J. Cole et al., “Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations,” European Respiratory Journal, vol. 40, no. 6, pp. 1324–1343, 2012. [29] R.A. Harris, S. K.Nishiyama, D.W.Wray, and R. S. Richardson, “Ultrasound assessment of flow-mediated dilation,” Hypertension, vol. 55, no. 5, pp. 1075–1085, 2010. [30] R. A. Harris, V. Tedjasaputra, J. Zhao, and R. S. Richardson, “Premenopausal women exhibit an inherent protection of endothelial function following a high-fat meal,” Reproductive Sciences, vol. 19, no. 2, pp. 221–228, 2012. [31] D. H. J. Thijssen, M. A. Black, K. E. Pyke et al., “Assessment of flow-mediated dilation in humans: a methodological and physiological guideline,” American Journal of Physiology- Heart and Circulatory Physiology, vol. 300, no. 1, pp. H2– H12, 2011. [32] J. Cohen, Statistical Power Analysis for the Behavioral Sciences, Erlbaum Associates, 2nd edition, 1988. [33] C. C. Derella, N. Lee, R. Crandall et al., “Assessment of endothelial function is reproducible in patients with cystic fibrosis,” Journal of Cystic Fibrosis, 2019. [34] R. G. Knowles and S. Moncada, “Nitric-oxide synthases in mammals,” Biochemical Journal, vol. 298, no. 2, pp. 249–258, 1994. [35] P. Pacher, J. S. Beckman, and L. Liaudet, “Nitric oxide and peroxynitrite in health and disease,” Physiological Reviews, vol. 87, no. 1, pp. 315–424, 2007. [36] C. Szabo, H. Ischiropoulos, and R. Radi, “Peroxynitrite: biochemistry, pathophysiology and development of therapeutics,” Nature Reviews Drug Discovery, vol. 6, no. 8, pp. 662–680, 2007. [37] V. K. Singh and S. J. Schwarzenberg, “Pancreatic insufficiency in cystic fibrosis,” Journal of Cystic Fibrosis, vol. 16, pp. S70– S78, 2017. [38] M. Scarpa, A. Rigo, M. Maiorino, F. Ursini, and C. Gregolin, “Formation of α-tocopherol radical and recycling of α-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes: an electron paramagnetic resonance study,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 801, no. 2, pp. 215–219, 1984. [39] S. D. Wollin and P. J. H. Jones, “α-Lipoic acid and cardiovascular disease,” The Journal of Nutrition, vol. 133, no. 11, pp. 3327–3330, 2003. [40] D. P. Xu and W. W. Wells, “α-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria,” Journal of Bioenergetics and Biomembranes, vol. 28, no. 1, pp. 77–85, 1996. [41] P. M. Vanhoutte, H. Shimokawa, E. H. C. Tang, and M. Feletou, “Endothelial dysfunction and vascular disease,” Acta Physiologica, vol. 196, no. 2, pp. 193–222, 2009. [42] Y. Inaba, J. A. Chen, and S. R. Bergmann, “Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis,” The International Journal of Cardiovascular Imaging, vol. 26, no. 6, pp. 631–640, 2010. [43] M. A. Tucker, B. Berry, N. Seigler et al., “Blood flow regulation and oxidative stress during submaximal cycling exercise in patients with cystic fibrosis,” Journal of Cystic Fibrosis, vol. 17, no. 2, pp. 256–263, 2018. [44] P. A. Nixon, D. M. Orenstein, S. F. Kelsey, and C. F. Doershuk, “The prognostic value of exercise testing in patients with cystic fibrosis,” The New England Journal of Medicine, vol. 327, no. 25, pp. 1785–1788, 1992. [45] P. Pianosi, J. Leblanc, and A. Almudevar, “Peak oxygen uptake and mortality in children with cystic fibrosis,” Thorax, vol. 60, no. 1, pp. 50–54, 2005.",
year = "2019",
month = "6",
day = "19",
doi = "10.1155/2019/1629638",
language = "English",
volume = "2019",
journal = "Oxidative Medicine and Cellular Longevity",
issn = "1942-0900",

}

Tucker, MA, Fox, BM, Seigler, N, Rodriquez-Miguelez, P, Looney, J, Thomas, J, McKie, KT, Forseen, C & Davison, G 2019, 'Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress', Oxidative Medicine and Cellular Longevity, vol. 2019. https://doi.org/10.1155/2019/1629638

Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress. / Tucker, Matthew A; Fox, Brandon M; Seigler, Nichole ; Rodriquez-Miguelez, Paula; Looney, Jacob; Thomas, Jeffrey; McKie, Kathleen T; Forseen, Caralee; Davison, Gareth.

In: Oxidative Medicine and Cellular Longevity, Vol. 2019, 19.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

AU - Tucker, Matthew A

AU - Fox, Brandon M

AU - Seigler, Nichole

AU - Rodriquez-Miguelez, Paula

AU - Looney, Jacob

AU - Thomas, Jeffrey

AU - McKie, Kathleen T

AU - Forseen, Caralee

AU - Davison, Gareth

N1 - [1] A. Cantin, “Cystic fibrosis lung inflammation: early, sustained, and severe,” American journal of Respiratory and Critical Care Medicine, vol. 151, no. 4, pp. 939–941, 1995. [2] M. Gruet, T. Troosters, and S. Verges, “Peripheral muscle abnormalities in cystic fibrosis: etiology, clinical implications and response to therapeutic interventions,” Journal of Cystic Fibrosis, vol. 16, no. 5, pp. 538–552, 2017. [3] B. J. Plant, C. H. Goss, W. D. Plant, and S. C. Bell, “Management of comorbidities in older patients with cystic fibrosis,” The Lancet Respiratory Medicine, vol. 1, no. 2, pp. 164–174, 2013. [4] D. S. Celermajer, K. E. Sorensen, V. M. Gooch et al., “Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis,” The Lancet, vol. 340, no. 8828, pp. 1111–1115, 1992. [5] T. Gori, S. Muxel, A. Damaske et al., “Endothelial function assessment: flow-mediated dilation and constriction provide different and complementary information on the presence of coronary artery disease,” European Heart Journal, vol. 33, no. 3, pp. 363–371, 2012. [6] A. Uehata, E. H. Lieberman, M. D. Gerhard et al., “Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery,” Vascular Medicine, vol. 2, no. 2, pp. 87–92, 1997. [7] D. Green, “Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function,” Journal of Applied Physiology, vol. 99, no. 3, pp. 1233-1234, 2005. [8] S. Poore, B. Berry, D. Eidson, K. T. McKie, and R. A. Harris, “Evidence of vascular endothelial dysfunction in young patients with cystic fibrosis,” Chest Journal, vol. 143, no. 4, pp. 939–945, 2013. [9] P. Rodriguez-Miguelez, J. Thomas, N. Seigler et al., “Evidence of microvascular dysfunction in patients with cystic fibrosis,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 310, no. 11, pp. H1479–H1485, 2016. [10] R. K. Brown and F. J. Kelly, “Role of free radicals in the pathogenesis of cystic fibrosis,” Thorax, vol. 49, no. 8, pp. 738– 742, 1994. [11] R. K. Brown, H. Wyatt, J. F. Price, and F. J. Kelly, “Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress,” European Respiratory Journal, vol. 9, no. 2, pp. 334– 339, 1996. [12] A. L. Coates, P. Boyce, D. Muller, M. Mearns, and S. Godfrey, “The role of nutritional status, airway obstruction, hypoxia, and abnormalities in serum lipid composition in limiting exercise tolerance in children with cystic fibrosis,” Acta Paediatrica, vol. 69, no. 3, pp. 353–358, 1980. [13] A. Lezo, F. Biasi, P. Massarenti et al., “Oxidative stress in stable cystic fibrosis patients: do we need higher antioxidant plasma levels?,” Journal of Cystic Fibrosis, vol. 12, no. 1, pp. 35–41, 2013. [14] P. Montuschi, P. Paredi, M. Corradi et al., “8-Isoprostane, a biomarker of oxidative stress, is increased in cystic fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 3, 1999. [15] A. Van Der Vliet, J. P. Eiserich, G. P. Marelich, B. Halliwell, and C. E. Cross, “Oxidative stress in cystic fibrosis: does it occur and does it matter?,” Advances in Pharmacology, vol. 38, pp. 491–513, 1996. [16] L. G. Wood, D. A. Fitzgerald, P. G. Gibson, D. M. Cooper, C. E. Collins, and M. L. Garg, “Oxidative stress in cystic fibrosis: dietary and metabolic factors,” Journal of the American College of Nutrition, vol. 20, no. 2, pp. 157–165, 2001. [17] G. Zalba, G. S. José, M..́ U. Moreno et al., “Oxidative stress in arterial hypertension: role of NAD(P)H oxidase,” Hypertension, vol. 38, no. 6, pp. 1395–1399, 2001. [18] F. Galli, A. Battistoni, R. Gambari et al., “Oxidative stress and antioxidant therapy in cystic fibrosis,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1822, no. 5, pp. 690–713, 2012. [19] R. A. Harris, S. K. Nishiyama, D. W. Wray, V. Tedjasaputra, D. M. Bailey, and R. S. Richardson, “The effect of oral antioxidants on brachial artery flow-mediated dilation following 5 and 10 min of ischemia,” European Journal of Applied Physiology, vol. 107, no. 4, pp. 445–453, 2009. [20] S. J. Ives, R. A. Harris, M. A. H. Witman et al., “Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox balance,” Hypertension, vol. 63, no. 3, pp. 459–467, 2014. [21] C. Sánchez-Moreno, M. P. Cano, B. de Ancos et al., “Consumption of high-pressurized vegetable soup increases plasma vitamin C and decreases oxidative stress and inflammatory biomarkers in healthy humans,” The Journal of Nutrition, vol. 134, no. 11, pp. 3021–3025, 2004. [22] D. W. Wray, S. K. Nishiyama, R. A. Harris et al., “Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption,” Hypertension, vol. 59, no. 4, pp. 818–824, 2012. [23] G. K. Kapuku, F. A. Treiber, H. C. Davis, G. A. Harshfield, B. B. Cook, and G. A. Mensah, “Hemodynamic function at rest, during acute stress, and in the field: predictors of cardiac structure and function 2 years later in youth,” Hypertension, vol. 34, no. 5, pp. 1026–1031, 1999. [24] S. P. Wolff, “[18] Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides,” Methods in Enzymology, vol. 233, pp. 182–189, 1994. [25] P. Medlow, J. McEneny, M. H. Murphy, T. Trinick, E. Duly, and G. W. Davison, “Exercise training protects the LDL I subfraction from oxidation susceptibility in an aged human population,” Atherosclerosis, vol. 239, no. 2, pp. 516–522, 2015. [26] D. L. Kellogg Jr, P. E. Pérgola, K. L. Piest et al., “Cutaneous active vasodilation in humans is mediated by cholinergic nerve cotransmission,” Circulation Research, vol. 77, no. 6, pp. 1222– 1228, 1995. [27] A. T. Society, “Standardization of Spirometry, 1994 Update. American Thoracic Society,” American Journal of Respiratory and Critical Care Medicine, vol. 152, no. 3, pp. 1107–1136, 1995. [28] P. H. Quanjer, S. Stanojevic, T. J. Cole et al., “Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations,” European Respiratory Journal, vol. 40, no. 6, pp. 1324–1343, 2012. [29] R.A. Harris, S. K.Nishiyama, D.W.Wray, and R. S. Richardson, “Ultrasound assessment of flow-mediated dilation,” Hypertension, vol. 55, no. 5, pp. 1075–1085, 2010. [30] R. A. Harris, V. Tedjasaputra, J. Zhao, and R. S. Richardson, “Premenopausal women exhibit an inherent protection of endothelial function following a high-fat meal,” Reproductive Sciences, vol. 19, no. 2, pp. 221–228, 2012. [31] D. H. J. Thijssen, M. A. Black, K. E. Pyke et al., “Assessment of flow-mediated dilation in humans: a methodological and physiological guideline,” American Journal of Physiology- Heart and Circulatory Physiology, vol. 300, no. 1, pp. H2– H12, 2011. [32] J. Cohen, Statistical Power Analysis for the Behavioral Sciences, Erlbaum Associates, 2nd edition, 1988. [33] C. C. Derella, N. Lee, R. Crandall et al., “Assessment of endothelial function is reproducible in patients with cystic fibrosis,” Journal of Cystic Fibrosis, 2019. [34] R. G. Knowles and S. Moncada, “Nitric-oxide synthases in mammals,” Biochemical Journal, vol. 298, no. 2, pp. 249–258, 1994. [35] P. Pacher, J. S. Beckman, and L. Liaudet, “Nitric oxide and peroxynitrite in health and disease,” Physiological Reviews, vol. 87, no. 1, pp. 315–424, 2007. [36] C. Szabo, H. Ischiropoulos, and R. Radi, “Peroxynitrite: biochemistry, pathophysiology and development of therapeutics,” Nature Reviews Drug Discovery, vol. 6, no. 8, pp. 662–680, 2007. [37] V. K. Singh and S. J. Schwarzenberg, “Pancreatic insufficiency in cystic fibrosis,” Journal of Cystic Fibrosis, vol. 16, pp. S70– S78, 2017. [38] M. Scarpa, A. Rigo, M. Maiorino, F. Ursini, and C. Gregolin, “Formation of α-tocopherol radical and recycling of α-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes: an electron paramagnetic resonance study,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 801, no. 2, pp. 215–219, 1984. [39] S. D. Wollin and P. J. H. Jones, “α-Lipoic acid and cardiovascular disease,” The Journal of Nutrition, vol. 133, no. 11, pp. 3327–3330, 2003. [40] D. P. Xu and W. W. Wells, “α-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria,” Journal of Bioenergetics and Biomembranes, vol. 28, no. 1, pp. 77–85, 1996. [41] P. M. Vanhoutte, H. Shimokawa, E. H. C. Tang, and M. Feletou, “Endothelial dysfunction and vascular disease,” Acta Physiologica, vol. 196, no. 2, pp. 193–222, 2009. [42] Y. Inaba, J. A. Chen, and S. R. Bergmann, “Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis,” The International Journal of Cardiovascular Imaging, vol. 26, no. 6, pp. 631–640, 2010. [43] M. A. Tucker, B. Berry, N. Seigler et al., “Blood flow regulation and oxidative stress during submaximal cycling exercise in patients with cystic fibrosis,” Journal of Cystic Fibrosis, vol. 17, no. 2, pp. 256–263, 2018. [44] P. A. Nixon, D. M. Orenstein, S. F. Kelsey, and C. F. Doershuk, “The prognostic value of exercise testing in patients with cystic fibrosis,” The New England Journal of Medicine, vol. 327, no. 25, pp. 1785–1788, 1992. [45] P. Pianosi, J. Leblanc, and A. Almudevar, “Peak oxygen uptake and mortality in children with cystic fibrosis,” Thorax, vol. 60, no. 1, pp. 50–54, 2005.

PY - 2019/6/19

Y1 - 2019/6/19

N2 - Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3%), compared to no change following placebo (Δ - 0.8 ± 1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 μM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 μM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

AB - Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n = 18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n = 9). In a subgroup of patients (n = 9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p = 0.032) increase in FMD was observed following AOC (Δ1.9 ± 3.3%), compared to no change following placebo (Δ - 0.8 ± 1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48 ± 2.91 vs. -1.98 ± 2.32 μM, p = 0.024) and tended to decrease LOOH (Δ - 0.2 ± 0.1 vs. 0.1 ± 0.1 μM, p = 0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

UR - http://www.scopus.com/inward/record.url?scp=85070069706&partnerID=8YFLogxK

U2 - 10.1155/2019/1629638

DO - 10.1155/2019/1629638

M3 - Article

VL - 2019

JO - Oxidative Medicine and Cellular Longevity

T2 - Oxidative Medicine and Cellular Longevity

JF - Oxidative Medicine and Cellular Longevity

SN - 1942-0900

ER -

Tucker MA, Fox BM, Seigler N, Rodriquez-Miguelez P, Looney J, Thomas J et al. Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress. Oxidative Medicine and Cellular Longevity. 2019 Jun 19;2019. https://doi.org/10.1155/2019/1629638