Red wine polyphenols correct vascular function injured by chronic carbon tetrachloride intoxication

The aim of the study was to evaluate the effect of red wine polyphenols extract Provinols™ on the development of cardiovascular injury in the model of carbon tetrachloride (CCl4) intoxication. We followed the thoracic aorta vasoactivity and left ventricle nitric oxide (NO) synthase activity in male Wistar rats. In the preventive experiment lasting for 12 weeks the control group, the group receiving CCl4 (0.5 ml/kg) two times a week subcutaneously, the group receiving Provinols™ (30 mg/kg/day) in drinking water and the group receiving CCl4+Provinols™ was used. In the recovery experiment, the initial 12 weeks of CCl4 treatment were followed by 3 weeks of spontaneous recovery or recovery with Provinols™. CCl4-intoxication resulted in the injury of vasoactivity which was demonstrated by the inhibition of acetylcholine-induced relaxation as well as noradrenaline-induced contraction. In the preventive as well as recovery experiment administration of polyphenols refreshed endothelium-dependent relaxant response and normalized inhibited contraction to adrenergic stimuli. Provinols™ treatment significantly increased NO-synthase activity in all groups. The results revealed beneficial effects of red wine polyphenols on vascular function injured by chronic CCl4 intoxication. The correction of endothelial function seems to be attributed to the activation of NO pathway by polyphenols

Dual effect of polyphenolic compounds on cardiac Na+/K+-ATPase during development and persistence of hypertension in ratsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

The enzyme kinetics of cardiac Na+/K+-ATPase were used for characterizing the ATP- and Na+-binding sites after administration of red wine polyphenolic compounds (Provinol) during developing and sustained hypertension. Hypertension was induced in rats (LN group) by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg–1·day–1). Provinol (40 mg·kg–1·day–1) was applied during developing hypertension (LNPF4 group) and sustained hypertension (LNPF7/3 group). Provinol reduced the number of active Na+/K+-ATPase molecules in cardiac tissue, as indicated by decreased Vmax values (by 33% in LNPF4 and 26% in LNPF7/3 compared with LN). Concerning qualitative properties of the enzyme, Provinol induced different effects on the ATP- and Na+-binding sites of Na+/K+-ATPase. The ATP-binding site was impaired by Provinol, as indicated by increased Km value (by 52% in LNPF4 vs. LN), suggesting worsened utilization of substrate by the enzyme. In sustained hypertension, however, Provinol had no..., On a utilisé la cinétique enzymatique de la Na+/K+-ATPase pour caractériser les sites de liaison de l’ATP et du Na+ après l’administration de composés polyphénoliques du vin rouge (Provinol) durant l’installation de l’hypertension et l’hypertension confirmée. On a induit l’hypertension chez des rats (groupe LN) par le biais de l’inhibiteur de la monoxyde d’azote synthase, l-NAME (40 mg·kg–1·jour–1). On a administré le Provinol (40 mg·kg–1·jour–1) durant l’installation de l’hypertension (LNPF4) et durant l’hypertension confirmée (LNPF7/3). Le Provinol a réduit le nombre de molécules actives de la Na+/K+-ATPase dans le tissu cardiaque, comme l’indique la diminution des valeurs de Vmax (de 33 % chez LNPF4 et de 26 % chez LNPF7/3 comparativement à celles du groupe LN). Du point de vue qualitatif, le Provinol a induit divers effets sur les sites de liaison de l’ATP et du Na+ de la Na+/K+-ATPase. Il a altéré le site de liaison de l’ATP, comme le montre l’augmentation de la valeur de Km (de 52 % chez le groupe L..

Red wine polyphenols prevent cyclosporine-induced nephrotoxicity at the level of the intrinsic apoptotic pathway

Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether Provinols flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with Provinols, or with CsA and Provinols simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. Provinols restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms

Red Wine Polyphenols Affect the Collagen Composition in the Aorta after Oxidative Damage Induced by Chronic Administration of CCl4

Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl4) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl4 for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenolssignificantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

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