Journal of Diabetes and Its Complications
Volume 24, Issue 6 , Pages 415-423 , November 2010

Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions

Received 13 October 2009 ,Revised 23 November 2009 ,Accepted 4 February 2010.

References 

  1. Al-Shabrawey M, Rojas M, Sanders T, Behzadian A, El-Remessy A, Bartoli M, et al. Role of NADPH oxidase in retinal vascular inflammation. Investigative Ophthalmology & Visual Science. 2008;49:3239–3244
  2. Anrather J, Racchumi G, Iadecola C. NF-kappaB regulates phagocytic NAD(P)H oxidase by inducing the expression of gp91phox. The Journal of Biological Chemistry. 2006;281:5657–5667
  3. Asaba K, Tojo A, Onozato ML, Goto A, Quinn MT, Fujita T, et al. Effects of NADPH oxidase inhibitor in diabetic nephropathy. Kidney International. 2005;67:1890–1898
  4. Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene. 2001;269:131–140
  5. Çınar MG, Ülker S, Alper G, Evinç A. Effect of dietary vitamin E supplementation on vascular reactivity of the thoracic aorta in streptozotocin-diabetic rats. Pharmacology. 2001;62:56–64
  6. Cotter MA, Cameron NE. Effect of the NAD(P)H oxidase inhibitor, apocynin, on peripheral nerve perfusion and function in diabetic rats. Life Sciences. 2003;73:1813–1824
  7. De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM. Endothelial dysfunction in diabetes. British Journal of Pharmacology. 2000;130:963–974
  8. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circulation Research. 2000;86:494–501
  9. Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1989;320:454–456
  10. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002;105:1656–1662
  11. Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R, et al. Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circulation Research. 2000;86:E85–E90
  12. Hamilton CA, Brosnan MJ, Al-Benna S, Berg G, Dominiczak AF. NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels. Hypertension. 2002;40:755–762
  13. Hayashi T, Juliet PA, Kano-Hayashi H, Tsunekawa T, Dingqunfang D, Sumi D, et al. NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent and -independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction. Diabetes, Obesity & Metabolism. 2005;7:334–343
  14. Heumüller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schröder K, et al. Apocynin is not an inhibitor of vascular NADPH oxidase but an antioxidant. Hypertension. 2008;51:211–217
  15. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circulation Research. 2001;88:E14–E22
  16. Kojda G, Harrison D. Interaction between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovascular Research. 1999;43:562–571
  17. Lopez-Lopez JG, Moral-Sanz J, Frazziano G, Gomez-Villalobos MJ, Flores-Hernandez J, Monjaraz E, et al. Diabetes induces pulmonary artery endothelial dysfunction by NADPH oxidase induction. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2008;295:L727–L732
  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. The Journal of Biological Chemistry. 1951;193:265–275
  19. Malta E, Schini V, Miller RC. Role of efficacy in the assessment of the actions of alpha-adrenoceptor agonists in rat aorta with endothelium. Journal of Pharmacy and Pharmacology. 1986;38:209–213
  20. Manea A, Manea SA, Gafencu AV, Raicu M, Simionescu M. AP-1-dependent transcriptional regulation of NADPH oxidase in human aortic smooth muscle cells. Role of p22phox subunit. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:878–885
  21. Marks-Konczalik J, Chu SC, Moss J. Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor-kB-binding sites. The Journal of Biological Chemistry. 1998;273:22201–22208
  22. Mayhan WG, Arrick DM, Sharpe GM, Patel KP, Sun H. Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial arterioles in type 1 diabetes mellitus. Microcirculation. 2006;13:567–575
  23. Matsumoto T, Kobayashi T, Wachi H, Seyama Y, Kamata K. Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Atherosclerosis. 2007;192:15–24
  24. McNally PG, Watt PA, Rimmer T, Burden AC, Hearnshaw JR, Thurston H. Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clinical Science (Lond). 1994;87:31–36
  25. McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992;35:771–776
  26. Pechánová O, Jendeková L, Vranková S. Effect of chronic apocynin treatment on nitric oxide and reactive oxygen species production in borderline and spontaneous hypertension. Pharmacological Reports. 2009;61:116–122
  27. Pieper GM, Moore-Hilton G, Roza AM. Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat. Life Sciences. 1996;58:PL147–PL152
  28. Ray A, Huisman MV, Tamsma JT, van Asten J, Bingen BO, Broeders EA, et al. The role of inflammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus. European Journal of Internal Medicine. 2009;20:253–260
  29. Riganti C, Costamagna C, Bosia A, Ghigo D. The NADPH oxidase inhibitor apocynin (acetovanillone) induces oxidative stress. Toxicology and Applied Pharmacology. 2006;212:179–187
  30. Riganti C, Costamagna C, Doublier S, Miraglia E, Polimeni M, Bosia A, et al. The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress. Toxicology and Applied Pharmacology. 2008;228:277–285
  31. Rueckschloss U, Galle J, Holtz J, Zerkowski HR, Morawietz H. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation. 2001;104:1767–1772
  32. Schleicher E, Friess U. Oxidative stress, AGE, and atherosclerosis. Kidney International Supplement. 2007;72:S17–S26
  33. Sorescu D, Weiss D, Lassègue B, Clempus RE, Szöcs K, Sorescu GP, et al. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation. 2002;105:1429–1435
  34. Srinivasan S, Hatley ME, Bolick DT, Palmer LA, Edelstein D, Brownlee M, et al. Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells. Diabetologia. 2004;47:1727–1734
  35. 't Hart BA, Simons JM, Knaan-Shanzer S, Bakker NP, Labadie RP. Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin. Free Radical Biology and Medicine. 1990;9:127–131
  36. Tomlinson KC, Gardiner SM, Hebden RA, Bennett T. Functional consequences of streptozotocin-induced diabetes mellitus, with particular reference to the cardiovascular system. Pharmacological Reviews. 1992;44:103–150
  37. Touyz RM. Apocynin, NADPH oxidase, and vascular cells: a complex matter. Hypertension. 2008;51:172–174
  38. Vejrazka M, Mícek R, Stípek S. Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells. Biochimica et Biophysica Acta. 2005;1722:143–147
  39. Wendt MC, Daiber A, Kleschyov AL, Mülsch A, Sydow K, Schulz E, et al. Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4. Free Radical Biology and Medicine. 2005;39:381–391

 The study was supported by the Turkish Diabetes Foundation and the Research Fund of Ege University (Project no: 03-TIP-013).

PII: S1056-8727(10)00020-6

doi: 10.1016/j.jdiacomp.2010.02.001

Journal of Diabetes and Its Complications
Volume 24, Issue 6 , Pages 415-423 , November 2010