Cited by 734Nitric Oxide and Endothelin EffectsAdvanced Glycation End Products researchAntioxidant Activity and Oxidative Stress

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New Insights on Oxidative Stress and Diabetic Complications May Lead to a “Causal” Antioxidant Therapy

Ceriello, Antonio·2003·Diabetes Care

DOI 10.2337/diacare.26.5.1589

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Abstract

Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. However, intervention studies with classic antioxidants, such as vitamin E, failed to demonstrate any beneficial effect. Recent studies demonstrate that a single hyperglycemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain seems to be the first and key event in the activation of all other pathways involved in the pathogenesis of diabetic complications. These include increased polyol pathway flux, increased advanced glycosylation end product formation, activation of protein kinase C, and increased hexosamine pathway flux. Superoxide overproduction is accompanied by increased nitric oxide generation, due to an endothelial NOS and inducible NOS uncoupled state, a phenomenon favoring the formation of the strong oxidant peroxynitrite, which in turn damages DNA. DNA damage is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase activation in turn depletes the intracellular concentration of its substrate NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, and produces an ADP-ribosylation of the GAPDH. These processes result in acute endothelial dysfunction in diabetic blood vessels that, convincingly, also contributes to the development of diabetic complications. These new findings may explain why classic antioxidants, such as vitamin E, which work by scavenging already-formed toxic oxidation products, have failed to show beneficial effects on diabetic complications and may suggest new and attractive “causal” antioxidant therapy. New low–molecular mass compounds that act as SOD or catalase mimetics or l-propionyl-carnitine and lipoic acid, which work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such a strategy, and preliminary studies support this hypothesis. This “causal” therapy would also be associated with other promising tools such as LY 333531, PJ34, and FP15, which block the protein kinase β isoform, poly(ADP-ribose) polymerase, and peroxynitrite, respectively. While waiting for these focused tools, we may have other options: thiazolinediones, statins, ACE inhibitors, and angiotensin 1 inhibitors can reduce intracellular oxidative stress generation, and it has been suggested that many of their beneficial effects, even in diabetic patients, are due to this property.

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The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus
(1993) · New England Journal of Medicine · doi:10.1056/nejm199309303291401 · Cited by 24,667
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07019-6 · Cited by 20,023
Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy
Brenner, B. M., Cooper, M. E., de Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H.-H., Remuzzi, G., Snapinn, S. M., Zhang, Z., & Shahinfar, S. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011161 · Cited by 7,493
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial
(2002) · The Lancet · doi:10.1016/s0140-6736(02)09327-3 · Cited by 6,992
Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes
Lewis, E. J., Hunsicker, L. G., Clarke, W. R., Berl, T., Pohl, M. A., Lewis, J. B., Ritz, E., Atkins, R. C., Rohde, R., & Raz, I. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011303 · Cited by 5,987
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol
Dahlöf, B., Devereux, R. B., Kjeldsen, S. E., Julius, S., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristiansson, K., Lederballe-Pedersen, O., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08089-3 · Cited by 5,407
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress
Cai, H., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.87.10.840 · Cited by 3,839
Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy
(2000) · The Lancet · doi:10.1016/s0140-6736(99)12323-7 · Cited by 3,179
Diabetes and Cardiovascular Disease: The Framingham Study
Kannel, W. B. (1979) · JAMA · doi:10.1001/jama.1979.03290450033020 · Cited by 2,936
Nitric oxide synthases: Roles, tolls, and controls
Nathan, C., & Xie, Q. W. (1994) · Cell · doi:10.1016/0092-8674(94)90266-6 · Cited by 2,920
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes
Parving, H.-H., Lehnert, H., Bröchner-Mortensen, J., Gomis, R., Andersen, S., & Arner, P. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011489 · Cited by 2,873
[Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes].
Parving, H., Lehnert, H., Brøchner‐Mortensen, J., Gomis, R., Andersen, S., & Arner, P. (2001) · PubMed · Cited by 2,527
Untitled work
(2000) · PubMed · Cited by 2,095
Oxidative Stress and Diabetic Vascular Complications
Giugliano, D., Ceriello, A., & Paolisso, G. (1996) · Diabetes Care · doi:10.2337/diacare.19.3.257 · Cited by 1,921
Self-citation
Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol
Lindholm, L. H., Ibsen, H., Dahlöf, B., Devereux, R. B., Beevers, G., de Faire, U., Fyhrquist, F., Julius, S., Kjeldsen, S. E., Kristiansson, K., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08090-x · Cited by 1,560
Pleiotropic Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors
Takemoto, M., & Liao, J. K. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1101.098486 · Cited by 1,274
Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus
Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M. P., Thaiss, F., Stahl, R. A. K., Warnholtz, A., et al. (2001) · Circulation Research · doi:10.1161/01.res.88.2.e14 · Cited by 1,191
Endothelial dysfunction in diabetes
De Vriese, A. S., Verbeuren, T. J., Van de Voorde, J., Lameire, N. H., & Vanhoutte, P. M. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703393 · Cited by 1,165
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation
Du, X.-L., Edelstein, D., Rossetti, L., Fantus, I. G., Goldberg, H. J., Ziyadeh, F. N., Wu, J., & Brownlee, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.22.12222 · Cited by 1,152
Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.
Johnstone, M. T., Creager, S. J., Scales, K. M., Cusco, J. A., Lee, B. K., & Creager, M. A. (1993) · Circulation · doi:10.1161/01.cir.88.6.2510 · Cited by 1,117
Antioxidant Therapy: A New Pharmacological Approach in Shock, Inflammation, and Ischemia/Reperfusion Injury
Cuzzocrea, S., Riley, D. P., Caputi, A. P., & Salvemini, D. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01484-4 · Cited by 1,087
Biological Tyrosine Nitration: A Pathophysiological Function of Nitric Oxide and Reactive Oxygen Species
Ischiropoulos, H. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0755 · Cited by 1,025
Mechanisms of Increased Vascular Superoxide Production in Human Diabetes Mellitus
Guzik, T. J., Mussa, S., Gastaldi, D., Sadowski, J., Ratnatunga, C., Pillai, R. G., & Channon, K. M. (2002) · Circulation · doi:10.1161/01.cir.0000012748.58444.08 · Cited by 979
Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus
McVeigh, G. E., Brennan, G. M., Johnston, G. D., McDermott, B. J., McGrath, L. T., Henry, W. R., Andrews, J. W., & Hayes, J. R. (1992) · Diabetologia · doi:10.1007/bf00429099 · Cited by 916
Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site
Du, X. L., Edelstein, D., Dimmeler, S., Ju, Q., Sui, C., & Brownlee, M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11235 · Cited by 907
Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.
Ting, H. H., Timimi, F. K., Boles, K., Creager, S. J., Ganz, P., & Creager, M. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118394 · Cited by 869
Myocardial Cell Death in Human Diabetes
Frustaci, A., Kajstura, J., Chimenti, C., Jakoniuk, I., Leri, A., Maseri, A., Nadal-Ginard, B., & Anversa, P. (2000) · Circulation Research · doi:10.1161/01.res.87.12.1123 · Cited by 796
High Glucose Increases Nitric Oxide Synthase Expression and Superoxide Anion Generation in Human Aortic Endothelial Cells
Cosentino, F., Hishikawa, K., Katušić, Z. S., & Lüscher, T. F. (1997) · Circulation · doi:10.1161/01.cir.96.1.25 · Cited by 762
Hyperglycemia and cardiovascular disease in type 2 diabetes.
Laakso, M. (1999) · Diabetes · doi:10.2337/diabetes.48.5.937 · Cited by 745
Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes
Chaturvedi, N., Sjolie, A.-K., Stephenson, J., Abrahamian, H., Keipes, M., Castellarin, A., Rogulja-Pepeonik, Ž., & Fuller, J. (1998) · The Lancet · doi:10.1016/s0140-6736(97)06209-0 · Cited by 738
Hyperglycemia rapidly suppresses flow-mediated endothelium- dependent vasodilation of brachial artery
Kawano, H., Motoyama, T., Hirashima, O., Hirai, N., Miyao, Y., Sakamoto, T., Kugiyama, K., Ogawa, H., & Yasue, H. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00168-0 · Cited by 676
Evidence for an Independent and Cumulative Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Endothelial Dysfunction and Oxidative Stress Generation: Effects of Short- and Long-Term Simvastatin Treatment
Ceriello, A., Taboga, C., Tonutti, L., Quagliaro, L., Piconi, L., Bais, B., Da Ros, R., & Motz, E. (2002) · Circulation · doi:10.1161/01.cir.0000027569.76671.a8 · Cited by 655
Self-citation
Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite
Zou, M., Shi, C., & Cohen, R. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14442 · Cited by 613
Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation
Soriano, F. G., Virág, L., Jagtap, P. G., Szabó, É., Mabley, J. G., Liaudet, L., Marton, A., Hoyt, D. G., Murthy, K. G. K., Salzman, A. L., et al. (2001) · Nature Medicine · doi:10.1038/83241 · Cited by 602
Resistance to endotoxic shock as a consequence of defective NF‐κB activation in poly (ADP‐ribose) polymerase‐1 deficient mice
Oliver, F. J., Murcia, J. M., Nacci, C., Decker, P., Andriantsitohaina, R., Muller, S., de la Rubia, G., Stoclet, J., & de MURCIA, G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.16.4446 · Cited by 583
Free radicals mediate endothelial cell dysfunction caused by elevated glucose
Tesfamariam, B., & Cohen, R. A. (1992) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1992.263.2.h321 · Cited by 558
Molecular aspects of lipoic acid in the prevention of diabetes complications
Packer, L., Kraemer, K., & Rimbach, G. (2001) · Nutrition · doi:10.1016/s0899-9007(01)00658-x · Cited by 556
Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion.
Collins, T. (1993) · PubMed · Cited by 524
Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite
Zou, M.-H., Shi, C., & Cohen, R. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214442 · Cited by 494
Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy
Takemoto, M., Node, K., Nakagami, H., Liao, Y., Grimm, M. F., Takemoto, Y., Kitakaze, M., & Liao, J. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13350 · Cited by 485
Enzymic mechanisms of superoxide production
Cross, A. R., & Jones, O. T. G. (1991) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(05)80140-9 · Cited by 468
Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress
Mercuri, F., Tonutti, L., Taboga, C., Ceriello, A., Assaloni, R., Motz, E., & Quagliaro, L. (2001) · Diabetologia · doi:10.1007/s001250100529 · Cited by 418
Self-citation
Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme.
Baek, K. J., Thiel, B. A., Lucas, S., & Stuehr, D. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36901-7 · Cited by 389
IGF-1 Overexpression Inhibits the Development of Diabetic Cardiomyopathy and Angiotensin II–Mediated Oxidative Stress
Kajstura, J., Fiordaliso, F., Andreoli, A. M., Li, B., Chimenti, S., Medow, M. S., Limana, F., Nadal‐Ginard, B., Leri, A., & Anversa, P. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1414 · Cited by 384
Peroxisome Proliferator-Activated Receptor γ-Dependent Repression of the Inducible Nitric Oxide Synthase Gene
Li, M., Pascual, G., & Glass, C. K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.13.4699-4707.2000 · Cited by 377
Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB
Onozato, M. L., Tojo, A., Goto, A., Fujita, T., & Wilcox, C. S. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.00123.x · Cited by 374
The AT 1 -Type Angiotensin Receptor in Oxidative Stress and Atherogenesis
Nickenig, G., & Harrison, D. G. (2002) · Circulation · doi:10.1161/hc0302.102618 · Cited by 367
Vascular Effects of Acute Hyperglycemia in Humans Are Reversed by l-Arginine: Evidence for Reduced Availability of Nitric Oxide During Hyperglycemia
Giugliano, D., Marfella, R., Coppola, L., Verrazzo, G., Acampora, R., Giunta, R., Nappo, F., Lucarelli, C., & D’Onofrio, F. (1997) · Circulation · doi:10.1161/01.cir.95.7.1783 · Cited by 360
Genetic Disruption of Poly (ADP-Ribose) Synthetase Inhibits the Expression of P-Selectin and Intercellular Adhesion Molecule-1 in Myocardial Ischemia/Reperfusion Injury
Zingarelli, B., Salzman, A. L., & Szabó, C. (1998) · Circulation Research · doi:10.1161/01.res.83.1.85 · Cited by 337
Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans
Beckman, J. A., Goldfine, A. B., Gordon, M. B., & Creager, M. A. (2001) · Circulation · doi:10.1161/01.cir.103.12.1618 · Cited by 314
Effect of Antioxidant Treatment of Streptozotocin-Induced Diabetic Rats on Endoneurial Blood Flow, Motor Nerve Conduction Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve
Coppey, L. J., Gellett, J. S., Davidson, E. P., Dunlap, J. A., Lund, D. D., & Yorek, M. A. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1927 · Cited by 300
Angiotensin II-induced superoxide anion generation in human vascular endothelial cells Role of membrane-bound NADH-/NADPH-oxidases
Zhang, H. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00183-2 · Cited by 296
The Role of Poly(ADP-Ribose) Polymerase Activation in the Development of Myocardial and Endothelial Dysfunction in Diabetes
Pacher, P., Liaudet, L., Soriano, F. G., Mabley, J. G., Szabó, É., & Szabó, C. (2002) · Diabetes · doi:10.2337/diabetes.51.2.514 · Cited by 281
Acute Hyperglycemia Induces Nitrotyrosine Formation and Apoptosis in Perfused Heart From Rat
Ceriello, A., Quagliaro, L., D’Amico, M., Filippo, C. D., Marfella, R., Nappo, F., Berrino, L., Rossi, F., & Giugliano, D. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1076 · Cited by 278
Self-citation
Inhibition of Protein Kinase Cβ Prevents Impaired Endothelium-Dependent Vasodilation Caused by Hyperglycemia in Humans
Beckman, J. A., Goldfine, A. B., Gordon, M. B., Garrett, L. A., & Creager, M. A. (2002) · Circulation Research · doi:10.1161/hh0102.102359 · Cited by 276
Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase
Szabó, C., Virág, L., Cuzzocrea, S., Scott, G. S., Hake, P. W., O’Connor, M., Zingarelli, B., Salzman, A. L., & Kun, E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3867 · Cited by 262
Role of Hyperglycemia in Nitrotyrosine Postprandial Generation
Ceriello, A., Quagliaro, L., Catone, B., Pascon, R., Piazzola, M., Bais, B., Marra, G., Tonutti, L., Taboga, C., & Motz, E. (2002) · Diabetes Care · doi:10.2337/diacare.25.8.1439 · Cited by 257
Self-citation
Cerivastatin, a Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor, Improves Endothelial Function in Elderly Diabetic Patients Within 3 Days
Tsunekawa, T., Hayashi, T., Kano, H., Sumi, D., Matsui‐Hirai, H., Thakur, N. K., Egashira, K., & Iguchi, A. (2001) · Circulation · doi:10.1161/hc2901.094094 · Cited by 256
Poly(ADP-Ribose) Synthetase Activation Mediates Mitochondrial Injury During Oxidant-Induced Cell Death
Virág, L., Salzman, A. L., & Szabó, C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.7.3753 · Cited by 246
Acute hyperglycemia induces an oxidative stress in healthy subjects
Marfella, R., Quagliaro, L., Nappo, F., Ceriello, A., & Giugliano, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13727 · Cited by 242
Self-citation
Are ACE Inhibitors a “Magic Bullet” Against Oxidative Stress?
Münzel, T. F., & Keaney, J. F. (2001) · Circulation · doi:10.1161/hc3801.095585 · Cited by 228
Obesity and cardiovascular disease: The Framingham study
Gordon, T., & Kannel, W. B. (1976) · Clinics in Endocrinology and Metabolism · doi:10.1016/s0300-595x(76)80026-6 · Cited by 210
Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy.
Ceriello, A., Morocutti, A., Mercuri, F., Quagliaro, L., Moro, M., Damante, G., & Viberti, G. C. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2170 · Cited by 209
Self-citation
Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals
Diederich, D. A., Skopec, J., Diederich, A., & Dai, F. X. (1994) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1994.266.3.h1153 · Cited by 199
L-Propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector
Vanella, A., Russo, A., Acquaviva, R., Campisi, A., Giacomo, C. D., Sorrenti, V., & Barcellona, M. L. (2000) · Cell Biology and Toxicology · doi:10.1023/a:1007638025856 · Cited by 194
Beneficial effects of α-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress
Heitzer, T. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00551-2 · Cited by 194
Rapid Reversal of the Diabetic Endothelial Dysfunction by Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase
Soriano, F. G., Pacher, P., Mabley, J. G., Liaudet, L., & Szabó, C. (2001) · Circulation Research · doi:10.1161/hh2001.097797 · Cited by 190
Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia
Sen, K., Misra, A., Kumar, A., & Pandey, R. M. (2002) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(01)00341-2 · Cited by 185
Endothelial Dysfunction and Oxidative Stress During Estrogen Deficiency in Spontaneously Hypertensive Rats
Waßmann, S., Bäumer, A. T., Strehlow, K., van Eickels, M., Grohé, C., Ahlbory, K., Rösen, R., Böhm, M., & Nickenig, G. (2001) · Circulation · doi:10.1161/01.cir.103.3.435 · Cited by 181
Part I: Pathogenetic Role of Peroxynitrite in the Development of Diabetes and Diabetic Vascular Complications: Studies With FP15, A Novel Potent Peroxynitrite Decomposition Catalyst
Szabó, C., Mabley, J. G., Moeller, S. M., Shimanovich, R., Pacher, P., Virág, L., Soriano, F. G., van Duzer, J. H., Williams, W., Salzman, A. L., et al. (2002) · Molecular Medicine · doi:10.1007/bf03402167 · Cited by 175
Antioxidant vitamins and prevention of cardiovascular disease: Epidemiological and clinical trial data
Marchioli, R., Schweiger, C., Levantesi, G., Tavazzi, L., & Valagussa, F. (2001) · Lipids · doi:10.1007/s11745-001-0683-y · Cited by 174
Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus
Mayhan, W. G. (1989) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1989.256.3.h621 · Cited by 170
Improvement of Endothelial Function by Chronic Angiotensin-Converting Enzyme Inhibition in Heart Failure
Varin, R., Mulder, P. G. H., Tamion, F., Richard, V. J., Henry, J., Lallemand, F., Lerebours, G., & Thuillez, C. (2000) · Circulation · doi:10.1161/01.cir.102.3.351 · Cited by 157
Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation
Soriano, F. G., Virág, L., & Szabó, C. (2001) · Journal of Molecular Medicine · doi:10.1007/s001090100236 · Cited by 157
Endothelium-Dependent Relaxation in Aorta of BB Rat
Meraji, S., Jayakody, L., SENARATNE, M. P. J., Thomson, A. B. R., & Kappagoda, T. C. (1987) · Diabetes · doi:10.2337/diab.36.8.978 · Cited by 155
A hydroxyl radical–like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease
Pennathur, S., Wagner, J. D., Leeuwenburgh, C., Litwak, K. N., & Heinecke, J. W. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11194 · Cited by 153
Vascular targets of redox signalling in diabetes mellitus
Spitaler, M. M., & Graier, W. F. (2002) · Diabetologia · doi:10.1007/s00125-002-0782-0 · Cited by 149
Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles
Bohlen, H. G., & Lash, J. M. (1993) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1993.265.1.h219 · Cited by 145
Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects
Marfella, R., Verrazzo, G., Acampora, R., La Marca, C., Giunta, R., Lucarelli, C., Paolisso, G., Ceriello, A., & Giugliano, D. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.6.e1167 · Cited by 129
Self-citation
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Authors: Ceriello, A.
Affiliations: University of Udine (IT)
Corresponding author: Ceriello, Antonio
ORCID: Ceriello, Antonio
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2003-05-01
Volume: 26
Issue: 5
Pages: 1589-1596
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/diacare.26.5.1589
OpenAlex: W2058550328
Cited by: 734
References: 102
Citations by year: 2026: 9 · 2025: 8 · 2024: 16 · 2023: 15 · 2022: 16 · 2021: 24 · 2020: 13 · 2019: 27 · 2018: 34 · 2017: 41 · 2016: 33 · 2015: 34 · 2014: 46 · 2013: 49 · 2012: 50
FWCI: 4.48
Type: journal article
Language: en
Open access: closed
Locations: Diabetes Care (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System (University of Udine) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: oxidative stress, diabetes complications, superoxide, mitochondrial electron transport chain, hyperglycemia, polyol pathway, advanced glycation end products, protein kinase C, hexosamine biosynthetic pathway, nitric oxide, peroxynitrite, DNA damage, poly(ADP-ribose) polymerase, NAD+ depletion, endothelial dysfunction, antioxidant therapy, superoxide dismutase mimetic, catalase mimetics, alpha-lipoic acid, PJ34, thiazolidinediones, statins, ACE inhibitors, angiotensin receptor blockers
MeSH terms: Antioxidants, Diabetes Mellitus, DNA Damage, Endothelium, Vascular, Humans, Hyperglycemia, Models, Biological, Oxidative Stress, Peroxynitrous Acid, Diabetes Complications

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New Insights on Oxidative Stress and Diabetic Complications May Lead to a “Causal” Antioxidant Therapy

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