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

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 Endothelial Damage Induced by CCl 4 Administration

Summary It became evident in the present study that carbon tetrachloride (CCl 4 ), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CCl 4 /kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 μl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl 4 treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5±0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl 4 did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl 4 may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl 4 . This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases

Histochemical localization of sialylated glycoconjugates with Tritrichomonas mobilensis lectin (TLM)

A new sialic acid-specific lectin from the colonic parasite of squirrel monkeys Tritrichomonas mobilensis (TML) was tested on human and mouse tissues for histochemical staining properties. There were no substantial differences in reactivity between frozen and formalin fixed paraffin sections. TML staining was blocked by preincubation with sialic acid or by sialidase digestion. TMLIanti-TML antibody histochemistry was identical with the TML-gold technique. The staining pattern was not blood group dependent. TML stained strongly the luminal membranes of normal vascular endothelium as well as endothelial neoplasms. Lymphatic vessels and capillaries of kidney glomeruli and lung alveolar septi were negative or only slightly positive. In parenchymatous organs luminal membrane positivity was dominant, preferably of cells lining ducts. Weak fine-granular cytoplasmic and basolateral membrane staining was also observed. Umbrella cells in transitional epithelium and basa1 layers of squamous epithelia showed strong reactivity with cell membranes. Mucin in respiratory epithelium was positive whereas gastrointestinal mucins failed to stain uniformly. Erythrocytes and most white blood cell types showed distinct membrane positivity. Acetylation or alkaline Odeacetylation of tissue sections did not substantially change TML reactivity. Oxidation, however, completely blocked TML staining except for respiratory epithelium and colonic mucin

Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia

Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered N~-nitro-L-arginine methyl ester (L NAME) for 4 weeks. A dose of 40 mgkgíday increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heartlbody weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14c]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14c]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with foca1 myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular media1 proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO