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  • Author: S. Jankyová x
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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®.

Abstract

We observed the changes in electrical activity, biometric and haemodynamic parameters of hearts in animals with experimental diabetes mellitus (DM). As well the effect of carvedilol, PycnogenolR and its combination with carvedilol on DM heart function was tested. DM was induced by streptozotocin over three sequential days at a dose of 25 mg/kg body weight i.p. We started therapy by suspension of carvedilol, PycnogenolR and their combination for six weeks. Blood pressure was measured using tail cuff plethysmography. ECG, haemodynamic and biometric parameters were measured in isolated hearts perfused according to the Langendorff. DM rats had increased systolic arterial blood pressure, thicker free wall of left ventricle but weakened myocardial contractility compared with controls. In contrast to controls, electrophysiological parameters showed prolonged QT interval and increased incidence of dysrhythmias in DM rats. The PycnogenolR administration induced regression of left ventricular hypertrophy, improved left ventriculi contraction and increased coronary flow; however, it did not improve the electrical activity of the myocardium compared with DM ones. Carvedilol also reversed the myocardial remodelling, shortened the duration of QT interval and suppressed the incidence of dysrhythmias. The common combination of drugs improved biometric and haemodynamic parameters compared with DM animals, however, not so significantly as monotherapy. On the other hand, the combination of carvedilol and PycnogenolR significantly reduced the duration of the QT interval and shortened the incidence of dysrhythmias. We can conclude that the administration of PycnogenolR effectively improved haemodynamic parameters, and carvedilol affected biometric parameters and also electrical parameters in DM animals. We observed the marked synergic effect of the combination of both drugs on the electrical activity of myocardium. This combination shortened the most pathologically prolonged QT interval and reduced the number of dysrhythmias.

The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its ability to improve endothelial dysfunction in diabetic animals. The aim of this study was to isolate from Pycnogenol® mixture its active compounds and compare their efficacy on observed parameters. Pycnogenol® mixture was fractioned by re-extracting with petroleum ether, chloroform, ethyl acetate and butanol, subsequently. Pycnogenol® mixture and fractions (butanolic, water, ethyl acetate) were administered during 6 weeks to diabetic rats. Blood glucose levels were assessed from the arterio-venous blood at the beginning of experiment and at the end of experiment. Endothelial dysfunction was evaluated as the contractile responses to phenylephrine and acetylcholine. The amount of collagen I and III was assessed from thoracic aorta after picrosirius red staining. For the confirmation of the changes on molecular level, we determinated endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90) expression from left ventricle. Overall, the result suggest, that fractions are not so effective on observed parameters as Pycnogenol® mixture itself, indicating synergistic effect of the plant constituents.