The efficacy of newly synthesised agent and natural antioxidant treatment in diabetic and hypertensive rats

S. Jankyová 1 , A. Adameová 1 , J. Slažneva 1 , J. Navarová 2 , V. Drobná 3 , J. Csollei 4 , and E. Račanská 1
  • 1 Department of Pharmacology and Toxicology Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic
  • 2 Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Science, Bratislava, Slovak Republic
  • 3 Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic
  • 4 Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic

The efficacy of newly synthesised agent and natural antioxidant treatment in diabetic and hypertensive rats

Hypertension that develops as the result of cardiovascular damage in diabetes is one of the serious complications of diabetes. The aim of this study was to evaluate the changes in levels of oxidative stress and in endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90) expressions after the treatment of diabetic rats with a newly synthesised heteroarylaminoethanolic derivative 4/1E with potentially beta-adrenergic blockade effects and a strong antioxidant Pycnogenol®. The treatment of 6-weeks duration was indicated in the group of diabetic Wistar rats (DL; streptozotocin (STZ) 3×25 mg/kg i.p.) and hypertensive rats (HL, STZ) with 4/1E in the dose 10 mg/kg i.p. or with Pycnogenol® (DP, HP) in the dose 20 mg/kg p.o. Animals in control groups (C, H, D) received vehiculum. The levels of oxidative stress were assessed in kidney andliver as the activity of N-acetyl-β-D-glucosaminidase (NAGA) and the levels of thiobarbituric acid reactive substances (TBARs). The expression of eNOS and Hsp90 was assessed from the hearts of all animals using SDS-Page and Western blotting.

In our study the effects of newly synthesised drug 4/1E and Pycnogenol® on the levels of oxidative stress were comparable only in diabetic animals. The expression of eNOS was decreased in diabetic, but not hypertensive animals. The treatment with 4/1E did not affect the expression of eNOS unlike the treatment with Pycnogenol® after which the expression was significantly increased. The expression of Hsp90 was increased in both hypertensive and diabetic animals. The treatment with 4/1E was more effective in decreasing Hsp90 expression in both groups of animals than the treatment with Pycnogenol®.

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  • HAMDEN, K. - BOUJBIHA, M. A. - MASMOUDI, H. - AYADI, F. M. - JAMOUSSI, K. - ELFEKI, A. Combined vitamins (C and E) and insulin improve oxidative stress and pancreatic and hepatic injury in alloxan diabetic rats. Biomed Pharmacother. 63, 2009, p. 95-109.

  • INOGUCHI, T. - SONTA, T. - TSUBOUCHI, H. - ETOH, T. - KAKIMOTO, M. - SONODA, N. a kol. Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes role of vascular NAD(P)H oxidase. J Am Nephrol. 14, 2003, p. S227-S232.

  • SHIBA, T. - INOGUCHI, T. - SPORTSMAN, J. R. - HEATH, W. F. - BURSELL, S. - KING, G. L. Correlation of diacylglycerol level and proteinkinase C activity in rat retina to retinal circulation. Am J Physiol. 265, 1993, p. E783-793.

  • RICHTER, K. - BUCHNER, J. Hsp90: chaperoning signal transduction. J Cell Physiol. 188, 2001, p. 281-290.

  • KOMATSUDA, A. - WAKUIL, H. - IMAI, H. - ITOH, H. - YASUDA, T. - MIURA, A. B. Expression of 90-kDa heat shock protein within regenerative tubular cells in a patient with acute oliguric renal failure due to malignant hypertension. Ren Fail. 21, 1999, p. 113-117.

  • PIECH, A. - DESSY, C. - HAVAUX, X. - FERON, O. - BALLIGAND, J. L. Differential regulation of nitric oxide synthases and their allosteric regulators in heart and vessels of hypertensive rats. Cardiovasc Res. 57, 2003, p. 456-67.

  • JAY, D. - HITOMI, H. - GRIENDLING, K. K. Oxidative stress and diabetic cardiovascular complications. Free Rad. Biol. Med. 40, 2006, p. 183-192.

  • JANKYOVÁ, S. - PREKOPOVÁ, K. - CSÖLLEI, J. - RAČANSKÁ, E. Analýza základných farmakologických vlastností novosyntetizovaných heteroarylaminoetanolov. Pokroky vo farmakológii v Slovenskej republike, Bratislava, 2009, p. 14-19.

  • LIU, X. - ZHOU, H. J. - ROHDEWALD, P. French Maritime Pine Bark Extract Pycnogenol Dose-Dependently Lowers Glucose in Type 2 diabetic Patients. Diabetes Care, 27, 2004, p. 893-896.

  • JANKYOVA, S. - KUCERA, P. - GOLDENBERG, Z. - YAGHI, D. - NAVAROVA, J. - KYSELOVA, Z. - STOLC, S. - KLIMAS, J. - RACANSKA, E. - MATYAS, S. Pycnogenol® Efficiency on Glycaemia, Motor Nerve Conduction Velocity and Markers of Oxidative Stress in Mild Type Diabetes in Rats. In press, Phytother. Res. 23, 2009, p. 1169-1174.

  • MARITIM, A. C. - DENE, B. A. - SANDERS, R. A. - WATKINS III, J. B. Effects of Pycnogenol Treatment on Oxidative Stress in Streptozotocin-Induced Diabetic Rats. J Biochem Molecular Toxicology, 17, 2003, p. 193-199.

  • WOOD, D. - DE BACKER, G. - FAERGEMAN, O. - GRAHAM, I. - MANCIA, G. - PYÖRÄLÄ, K. Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Eur Heart J, 19, 1998, p. 1434-1503.

  • COSENTINO, F. - HISHIKAWA, K. - KATUSIC, Z. S. - LÜSCHER, T. F. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 96, 1997, p. 25-28.

  • SRINIVASAN, S. - HATLEY, M. E. - BOLICK, D. T. - PALMER, L. A. - EDELSTEIN, D. - BROWNLEE, M. - HEDRICK, C. C. Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells. Diabetologia. 47, 2004, p. 1727-1734.

  • STALKER, T. J. - SKVARKA, C. B. - SCALIA, R. A novel role for calpains in the endothelial dysfunction of hyperglycemia. FASEB J. 17, 2003, p. 1511-1523.

  • HEITZER, T. - BROCKHOFF, C. - MAYER, B. - WARNHOLTZ, A. - MOLLNAU, H. - HENNE, S. - MEINERTZ, T. - MÜNZEL, T. Tetrahydrobiopterin improves endothelium-dependent vasodilatation in chronic smokers: evidence for a dysfunctional nitric oxide synthase. Circ Res. 86, 2000, p. E36-41.


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