Біологічні студії (Dec 2013)
Lipoflavon® application for pharmacological correction of endothelial dysfunction in diabetic rats
Abstract
It is known that endothelial dysfunction is one of the major factors in development of diabetic cardio-vascular complications. Besides, pathophysiological linkages between high concentration of glucose and vascular dysfunction remain not fully established. The aim of this study was to investigate acetylcholine-induced endothelium-dependent dilation of vascular segments obtained from healthy rats and incubated in hyperglycemic solution and vascular segments from diabetic rats before and after quercetin-filled phosphatidylcholine liposomes (Lipoflavon®) treatment in both in vitro and in vivo conditions. Changes in vascular tone were registered in isometric mode. Data are presented as mean ± SEM with “n” indicating the number of vascular preparations tested. On the day of the experiment diabetic rats showed four times higher blood glucose level and decreased dilation responses to acetylcholine (ACh, 1 nM–10 mM) of aortic rings precontracted with noradrenaline (NA, 1 mM)as compared to controls. Incubation of vascular rings under hyperglycemic (25 mM/L glucose) conditions led to time-dependent impairment of dilation responses as compared to normoglycemic (5.5 mM/L glucose) conditions. Lipoflavon® (3 µg/mL of quercetin) application to the organ bath with diabetic rats precontracted vascular rings resulted in a significant reduction in vascular tension. Being added on the plateau of Lipoflavon® relaxation, ACh showed increased dilation responses in comparison to diabetic tissues without Lipoflavon® application. Intravenous Lipoflavon® injections to diabetic rats in concentrations 15 mg/kg or 50 mg/kg of phosphatidylcholine restored dilatation responses up to the control level. In conclusion, we confirmed that hyperglycemia is one of the main factors leading to impairment of endothelium-dependent vasodilation. Quercetin-filled phosphatidylcholine liposomes significantly improve endothelium-dependent relaxation of isolated vascular rings from diabetic rats. We assume that Lipoflavon® is perspective in treatment of diabetic angiopathies.
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