Position Title
Research Associate
Education
- M.S., Chemistry, University of Buenos Aires
- Ph.D., Chemistry, University of Buenos Aires
Research Interests
Dr. Fraga's research program centers on the putative beneficial effects of plant-derived polyphenolic compounds against degenerative disorders, including cardiovascular disease and certain cancers. In this context, his work focuses on the biological properties of flavonoids and their respective in vivo metabolites. Emphasis is placed on studying the impact of these compounds on oxidative defense systems and tissue/cell oxidative damage. The methods employed encompass biochemical, physiological, molecular biological and analytical techniques and involve in vivo animal models as well as various cell culture systems.
Selected Publications
Fraga CG, Oteiza PI, Galleano M. Plant bioactives and redox signaling: (-)-Epicatechin as a paradigm. Mol Aspects Med. 2018 Feb 10. pii: S0098-2997(18)30002-5. [PubMed]
Oteiza PI, Fraga CG, Mills DA, Taft DH. Flavonoids and the gastrointestinal tract: Local and systemic effects. Mol Aspects Med. 2018 Jan 12. pii: S0098-2997(17)30159-0. [PubMed]
Cremonini E, Mastaloudis A, Hester SN, Verstraeten SV, Anderson M, Wood SM, Waterhouse AL, Fraga CG, Oteiza PI. Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity. Food Funct. 2017 Aug 1;8(8):2915-2923. [PubMed]
Cremonini E, Bettaieb A, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys. 2016 Jun 1;599:13-21. [PubMed]
Prince PD, Lanzi CR, Toblli JE, Elesgaray R, Oteiza PI, Fraga CG, Galleano M. Dietary (-)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats. Free Radic Biol Med. 2015 Nov 10;90:35-46. [PubMed]
Verstraeten SV, Fraga CG, Oteiza PI. Interactions of flavan-3-ols and procyanidins with membranes: mechanisms and the physiological relevance. Food Funct 2015;6(1):32-41. [PubMed]
Piotrkowski B, Calabro V, Galleano M, Fraga CG. (-)-Epicatechin prevents alterations in the metabolism of superoxide anion and nitric oxide in the hearts of L-NAME-treated rats. Food Funct 2015;6(1):155-61. [PubMed]
Litterio MC, Vazquez Prieto MA, Adamo AM, Elesgaray R, Oteiza PI, Galleano M, Fraga CG. (-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability. J Nutr Biochem 2015;26(7):745-51. [PubMed]
Lupton JR, Atkinson SA, Chang N, Fraga CG, Levy J, Messina M, Richardson DP, van Ommen B, Yang Y, Griffiths JC, Hathcock J. Exploring the benefits and challenges of establishing a DRI-like process for bioactives. Eur J Nutr 2014;53 Suppl 1:1-9. [PubMed]
Fraga CG, Oteiza PI, Galleano M. In vitro measurements and interpretation of total antioxidant capacity. Biochim Biophys Acta 2014;1840(2):931-4. [PubMed]
Bettaieb A, Vazquez Prieto MA, Rodriguez Lanzi C, Miatello RM, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic Biol Med 2014;72:247-56. [PubMed]
Verstraeten SV, Jaggers GK, Fraga CG, Oteiza PI. Procyanidins can interact with Caco-2 cell membrane lipid rafts: involvement of cholesterol. Biochim Biophys Acta 2013;1828(11):2646-53. [PubMed]
Galleano M, Bernatova I, Puzserova A, Balis P, Sestakova N, Pechanova O, Fraga CG. (-)-Epicatechin reduces blood pressure and improves vasorelaxation in spontaneously hypertensive rats by NO-mediated mechanism. IUBMB Life 2013;65(8):710-5. [PubMed]
Vazquez-Prieto MA, Bettaieb A, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin prevents TNFalpha-induced activation of signaling cascades involved in inflammation and insulin sensitivity in 3T3-L1 adipocytes. Arch Biochem Biophys 2012;527(2):113-8. [PubMed]
Litterio MC, Jaggers G, Sagdicoglu Celep G, Adamo AM, Costa MA, Oteiza PI, Fraga CG, Galleano M. Blood pressure-lowering effect of dietary (-)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels. Free Radic Biol Med 2012;53(10):1894-902. [PubMed]
Galleano M, Calabro V, Prince PD, Litterio MC, Piotrkowski B, Vazquez-Prieto MA, Miatello RM, Oteiza PI, Fraga CG. Flavonoids and metabolic syndrome. Ann N Y Acad Sci 2012;1259:87-94. [PubMed]
Da Silva M, Jaggers GK, Verstraeten SV, Erlejman AG, Fraga CG, Oteiza PI. Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells. Free Radic Biol Med 2012;52(1):151-9. [PubMed]
Fraga CG, Oteiza PI. Dietary flavonoids: Role of (-)-epicatechin and related procyanidins in cell signaling. Free Radic Biol Med 2011;51(4):813-23. [PubMed]
Fraga CG, Litterio MC, Prince PD, Calabro V, Piotrkowski B, Galleano M. Cocoa flavanols: effects on vascular nitric oxide and blood pressure. J Clin Biochem Nutr 2011;48(1):63-7. [PubMed]
Galleano M, Verstraeten SV, Oteiza PI, Fraga CG. Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Arch Biochem Biophys 2010;501(1):23-30. [PubMed]
Galleano M, Pechanova O, Fraga CG. Hypertension, nitric oxide, oxidants, and dietary plant polyphenols. Curr Pharm Biotechnol 2010;11(8):837-48. [PubMed]
Fraga CG, Galleano M, Verstraeten SV, Oteiza PI. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med 2010;31(6):435-45. [PubMed]
M. Galleano, S. V. Verstraeten, P. I. Oteiza, and C. G. Fraga. Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Archives of Biochemsitry and Biophyisics 2010 Apr 10. [Epub ahead of print] [PubMed]
M. Galleano, P. I. Oteiza, and C. G. Fraga. Cocoa, chocolate, and cardiovascular disease. Journal of Cardiovascular Pharmacology 54:483-490 (2009) [PubMed]
S. V. Verstraeten, C. G. Fraga, and P. I. Oteiza. Flavonoids-membrane interactions: consequences on membrane-associated processes, in Plant Phenolics and Human Health: Biochemistry, Nutrition, and Pharmacology, edited by C. G. Fraga. The Wiley-IUBMB Series on Biochemistry and Molecular Biology, pp. 107-136 (2009)
C. G. Fraga, G. Sagdicoglu Celep, and M. Galleano. Thermodynamics and kinetics: limitations for biochemical actions of plant polyphenols, in Plant Phenolics and Human Health: Biochemistry, Nutrition, and Pharmacology, edited by C. G. Fraga. The Wiley-IUBMB Series on Biochemistry and Molecular Biology, pp. 91-106 (2009)
G. G. Mackenzie, J. M. Delfino, C. L. Keen, C. G. Fraga and P. I. Oteiza. Dimeric procysnidins are inhibitors of NF-κB-DNA binding. Biochemical Pharmacology 78:1252-1262 (2009) [PubMed]
E. Herrera, R. Jiménez, O. I. Aruoma, S. Hercberg, I. Sánchez-García and C. G. Fraga. Antioxidant foods and health. Nutrition Reviews 67:S140-S145 (2009)
B. Piotrkowski, O. R. Koch, E. M. V. de Cavanagh, and C. G. Fraga. Cardiac mitochondria function and tissue remodeling are improved by a non-antihypertensive dose of enalapril in spontaneously hypertensive rats. Free Radical Research 43:390-399 (2009) [PubMed]
C. G. Fraga, and P. I. Oteiza. Flavanols and NF-κB activation: relevance for inflammation and associated diseases. In Dietary Modulation of Cell Signaling Pathways, edited by Y-J. Surh, Z. Dong, E. Cadenas, and L. Packer, CRC Press, Boca Raton, FL, pp 137-151 (2009)
S. V. Verstraeten, G. G. Mackenzie, P. I. Oteiza, and C. G. Fraga. (-)-Epicatechin and related procyanidins modulate intracellular calcium and prevent oxidation in Jurkat T cells. Free Radical Research 42: 864-872 (2008) [PubMed]
C. G. Fraga, and P. I. Oteiza. Flavanols and procyanidins, reactive oxygen species and NF-κB activation: relevance for disease. In Free Radicals in Pathophysiology, edited by: S. Alvarez, P. Evelson. Research Signpost, Transworld Research Network, Trivandrum, Kerala, India, pp 113-128 (2008)
A. G. Erlejman, G. Jaggers, C. G. Fraga, and P. I. Oteiza. Hexameric procyanidins inhibit TNFα-induced NF-κB activation in Caco-2 cells. Archives of Biochemistry and Biophysics 476:186-195 (2008) [PubMed]
E. M. V. de Cavanagh, J. E. Toblli, L. Ferder, Bárbara Piotrkowski, I. Stella, F. Inserra, and C. G. Fraga. Renal mitochondrial impairment is attenuated by AT1-blockade in experimental type-1 diabetes. American Journal of Physiology-Heart and Circulatory Physiology 294:456-465 (2008) [PubMed]
C. G. Fraga. Flavonoids: antioxidants in vitro. Nutritional antioxidants in vivo? IUBMB Life 59:308-315 (2007) [PubMed]
J. Milei, P. Forcada, C. G. Fraga, D. R. Grana, G. Ianelli, M. Chiarello, I. Trito, and G. Ambrosio. Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion. Cardiovascular Research 73:710-719 (2007) [PubMed]
B. Piotrkowski, C. G. Fraga and E. M. V. de Cavanagh. Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney. American Journal of Physiology-Regulatory, Integrative, and Comparative Physiology 292:1497-1501 (2007) [PubMed]
E. M. V. de Cavanagh, B. Piotrkowski and C. G. Fraga. Angiotensin II blockade and mitochondrial function: role in the retardation of aging. Frontiers in Biosciences 12:1049-1062 (2007) [PubMed]
G. G. Mackenzie, N. Queisser, M. L. Wolfson, C. G. Fraga, A. M. Adamo, and P. I. Oteiza. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active NF-κB and JAK-STAT pathways in Hodgkin’s lymphoma cells. International Journal of Cancer 123:56-65 (2006) [PubMed]
J. Ottaviani, C. L. Keen, and C. G. Fraga. Potential health benefits of cocoa flavanols for hypertension. In Proceedings 4th Malasyan International Cocoa Conference, edited by G. Denamany, K. H. Lamin, A. Ling, N. Maisin, A. C. Ahmad, S. Bakar, and N. M. Yazik. Malaysian Cocoa Board (2006)
C. G. Fraga, C. L. Keen, and J. Ottaviani. El chocolate y la salud. Sobre los efectos vasculares de los flavonoides del cacao. Antioxidantes: vitaminas y nutrientes 1(5):2-7 (2006). Published on line: Chocolate and health. On the vascular effects of flavanols in cocoa.
S. Das, C. G. Fraga, and D. K. Das. Cardioprotective effect of resveratrol via HO-1 expression involves p38 map kinase and PI-3-kinase signaling, but does not involve NF-κB. Free Radical Research 40:1066-1075 (2006) [PubMed]
A. Erlejman, C. G. Fraga, and P. I. Oteiza. Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage. Free Radical Biology and Medicine 41:1247-1256 (2006) [PubMed]
J. Ottaviani, C. L. Keen, and C. G. Fraga. Chocolate and health. On the vascular effects of flavanols in cocoa. Agro FOOD Industry High-tech 17:IX-XII (2006)
L. Actis-Goretta, J. I. Ottaviani and C. G. Fraga. Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. Journal of Agricultural and Food Chemistry 54:229-234 (2006) [PubMed]
E. M. V. de Cavanagh, J. E. Toblli, L. Ferder, B. Piotrkowski, I. Stella, C. G. Fraga and F. Inserra. Angiotensin II blockade improves mitochondrial function in spontaneous hypertensive rats. Cellular and Molecular Biology 51:573-578 (2005)
J. I. Ottaviani, L. Actis-Goretta, J. J. Villordo, and C. G. Fraga. Procyanidin structure defines the extent and specificity of angiotensin I converting enzyme inhibition. Biochimie 88:359-365 (2006) (Epub Oct 26, 2005) [PubMed]
C. G. Fraga. Relevance, essentality and toxicity of trace elements in human health. Molecular Aspects of Medicine 26: 235-244 (2005) [PubMed]
C. G. Fraga, P. I. Oteiza, C. L. Keen. Trace elements in human health. Molecular Aspects of Medicine 26: 233-234 (2005) [PubMed]
S. V. Verstraeten, J. F. Hammerstone, C. L. Keen, C. G. Fraga and P. I. Oteiza. Antioxidant and membrane effects of procyanidin dimers and trimers isolated from peanut and cocoa. Journal of Agricultural and Food Chemistry 53:5041-5048 (2005) [PubMed]
C. L. Keen, R. R. Holt, P. I. Oteiza, C. G. Fraga, and H. H. Schmitz. Cocoa antioxidants and cardiovascular health. American Journal of Clinical Nutrition 81: 298S-303S (2005) [PubMed]
P. I. Oteiza, S. V. Verstraeten, A. G. Erlejman, C. L. Keen, and C. G. Fraga. Flavonoid-membrane interactions: a protective role of flavonoids at the membrane surface? Clinical and Developmental Immunology 12:19-25 (2005) [PubMed]
C. G. Fraga, L. Actis-Goretta, F. Carrasquedo, S. B. Lotito, J. I. Ottaviani, S. A. Lazarus, H. H. Schmitz, and C. L. Keen. Regular consumption of a flavonoid-rich chocolate improved markers of cardiovascular health and oxidant stress in young soccer players. Clinical and Developmental Immunology 12:11-17 (2005) [PubMed]
C. G. Fraga. Cocoa, diabetes and hypertension: should we eat more chocolate? American Journal of Clinical Nutrition 81:541-542 (2005) [PubMed]
A. G. Erlejman, S. V. Verstraeten, C. G. Fraga, and P. I. Oteiza. The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radical Research 38:1311-1320 (2004) [PubMed]
L. Actis-Goretta, F. Carrasquedo, and C. G. Fraga. The regular supplementation with an antioxidant mixture decrease oxidative stress in healthy humans. Gender effect. Clinica Chimica Acta 349: 97-103 (2004) [PubMed]
S. V. Verstraeten, P. I. Oteiza, and C. G. Fraga. Membrane effects of cocoa procyanidins in liposomes and Jurkat T cells. Biological Research. 37: 293-300 (2004) [PubMed]
J. Milei, C. G. Fraga, D. R. Grana, R. Ferreira, and G. Ambrosio. Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury. Journal of the American College of Cardiology 43:2329-2336 (2004) [PubMed]
E. M. V. de Cavanagh, B. Piotrkowski, and C. G. Fraga. Concerted action of the renin-angiotensin system, mitochondria, and antioxidant defenses in aging. Molecular Aspects of Medicine 25: 27-36 (2004) [PubMed]
C. G. Fraga, and A. Boveris. Oxidative stress in aging and disease (editorial). Molecular Aspects of Medicine 25: 1-4 (2004) [PubMed]
M. Sato, C. G. Fraga, and D. K. Das. Induction of the expression of cardio-protective proteins after mild-to-moderate consumption of alcohol. Pathophysiology 10: 139-145 (2004) [PubMed]
G. G. Mackenzie, F. Carrasquedo, J. M. Delfino, C. L. Keen, C. G. Fraga, and P. I. Oteiza. Epicatechin, catechin and dimeric procyanidins inhibit PMA-induced NF-B activation at multiple steps in Jurkat T cells. FASEB Journal 18: 167-169 (2004) (Epub 2003 Nov 20). [PubMed]
L. Actis-Goretta, J. I. Ottaviani, C. L. Keen, and C. G. Fraga. Inhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and procyanidins. FEBS Letters 555: 597-600 (2003) [PubMed]
R. Ferreira, C. G. Fraga, F. Carrasquedo, H. Hourquebie, D. Grana, and J. Milei. Comparison between warm blood and crystalloid cardioplegia during open heart surgery. International Journal of Cardiology 90: 253-260 (2003) [PubMed]
C. G. Fraga, and C. L. Keen. Flavanols and procyanidins as modulators of oxidation in vitro and in vivo. In Free Radicals, Nitric Oxide, and Inflammation: Molecular, Biochemical, and Clinical Aspects (A. Tomasi, T. Ozben, and V. P. Skulachev, editores, NATO Science Series, Vol. 344, IOS Press, Netherlands), pp 24-33 (2003)
E. M. V. de Cavanagh, B. Piotrkowski, N. Basso, I. Stella, F. Inserra, L. Ferder, and C. G. Fraga. Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB Journal 17: 1096-1098 (2003) (Epub 2003 Apr 22) [PubMed]
S. V. Verstraeten, C. L. Keen, H. H. Schmitz, C. G. Fraga, and P. I. Oteiza. Flavonoid-liposome membrane interactions. Free Radical Biology and Medicine 34: 84-92 (2003) [PubMed]
D. Wilhelm Filho, F. Sell, L. Ribeiro, M. Ghislandi, F. Carrasquedo, C. G. Fraga, J. P. Wallauer, P. C. Simoes-Lopes, and M. M. Uhart. A comparison between the antioxidant status of terrestrial and diving mammals. Comparative Biochemistry and Physiology Part A 133: 885-892 (2002) [PubMed]
C. G. Fraga, and P. I. Oteiza. Iron toxicity and antioxidant nutrients. Toxicology 180: 23-32 (2002) [PubMed]
J. I. Ottaviani, F. Carrasquedo, C. L. Keen, S. A. Lazarus, H. H. Schmitz, and C. G. Fraga. Influence of cocoa-derived flavanols and procyanidins on UV-C mediated formation of 8-oxo-7,8-dehydro-2'-deoxyguanosine in isolated DNA. Archives of Biochemistry and Biophysics 406: 203-208 (2002) [PubMed]
R. R. Holt, S. A. Lazarus, M. C. Sullards, Q. Y. Zhu, D. D. Schramm, J. F. Hammerstone, C. G. Fraga, H. H. Schmitz, and C. L. Keen. Dimeric procyanidins in human plasma after the consumption of a flavanol -rich cocoa. American Journal of Clinical Nutrition 76: 798-804 (2002) [PubMed]
E. M. V. de Cavanagh, A. E. Honneger, E. Hofer, R. H. Bordenave, E. O. Bullorsky, N. A. Chasseing, and C. G. Fraga. Higher oxidation and lower antioxidant levels in periphereal blood plasma and bone marrow plasma from advanced cancer patients. Cancer 94: 3247-3252 (2002) [PubMed]
E. M. V. de Cavanagh, F. Inserra, J. Toblli, I. Stella, C. G. Fraga, and L. Ferder. Enalapril attenuates oxidative stress in diabetic rats. Hypertension 38: 1130-1136 (2001) [PubMed]
C. G. Fraga, J. F. Hammerstone, S. A. Lazarus, H. H. Schmitz, and C. L. Keen. More antioxidants in cocoa (letter to the editor). Journal of Nutrition 131: 835 (2001)
D. Wilhelm Filho, M. A. Torres, J. L. Marcon, C. G. Fraga, and A. Boveris. Comparative antioxidant defences in vertebrates-emphaiss on fish and mammals. Trends in Comparative Biochemistry and Physiology 7: 33-45 (2000)
S. B. Lotito, and C. G. Fraga. Ascorbate protects (+)-catechin from oxidation both in a pure chemical system and human plasma. Biological Research 33: 151-157 (2000) [PubMed]
R. Filip, S. B. Lotito, G. Ferraro, and C. G. Fraga. Antioxidant activity of Ilex paraguariensis and related species. Nutrition Research 20: 1437-1446 (2000)
S. B. Lotito, and C. G. Fraga. Catechins delayed alpha-tocopherol and beta-carotene depletion but did not affect ascorbate depletion in human plasma. Proceedings of the Society of Experimental Biology and Medicine 225: 32-38 (2000)
S. B. Lotito, L. Actis-Goretta, M. L. Renart, M. Caligiuri, D. Rein, H. H. Schmitz, F. M. Steimberg, C. L. Keen, and C. G. Fraga. Influence of oligomer chain length on the antioxidant activity of procyanidins. Biochemical and Biophysical Research Communications 276: 945-951 (2000) [PubMed]
V. B. C. Junqueira, F. Carrasquedo, L. A. Azzalis, K. A. S. Giavarotti, L. Givarotti, L. Rodrigues, C. G. Fraga, A. Boveris, and L. A. Videla. Content of liver and brain ubiquinol-9 and ubiquinol-10 after chronic ethanol intake in rats subjected to two levels of dietary alpha-tocopherol. Free Radical Research. 33: 313-319 (2000) [PubMed]
J. F. Wang, D. D. Schramm, R. R. Holt, J. L. Ensunsa, C. G. Fraga, H. H. Schmitz, and C. L. Keen. A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. Journal of Nutrition 130: 2115S-2119S (2000) [PubMed]
D. Rein, S. Lotito, R. R. Holt, C. L. Keen, H. H. Schmitz, and C. G. Fraga. Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma antioxidant capacity. Journal of Nutrition 130: 2109S-2114S (2000) [PubMed]
E. M. V. de Cavanagh, F. Inserra, L. Ferder, and C. G. Fraga. Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. American Journal of Physiology 278: R572-R577 (2000) [PubMed]