Protection of the vascular endothelium in experimental situations

One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo

Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta

Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by α1-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A23187-induced relaxations but also the catalase sensitive hydrogen peroxide (H2O2) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O2 •–) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe2SO4/H2O2-produced hydroxyl radical (•OH) and H2O2. Thus O2 •– produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did •OH and H2O2. In the large (conduit) artery, the effects of activated neutrophils and various ROS (O2 •–, •OH and H2O2) seem to be more dependent on muscle tension than on endothelial mechanisms

Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res

Summary Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increase

Effect of high-fat-fructose diet on synaptic plasticity in hippocampus and lipid profile of blood serum of rat: pharmacological possibilities of affecting risk factors

The aim of this study was to determine pharmacological possibilities of influencing the risk factors of metabolic syndrome (MetS). Hypertriacylglycerolemic (HTG) rats fed with high-fat-fructose diet (HFFD) were used as a model of the MetS. Wistar rats fed with standard diet were used as negative control group. HTG rats fed with HFFD for 8 weeks were used as positive control group. The effects of atorvastatin and SMe1EC2 were tested. The compounds were administered to the HTG rats after 5 weeks of HFFD, once a day for 3 weeks. After 8 weeks, the blood serum lipid profile and electrophysiology of neurotransmission in hippocampal sections were evaluated in vitro. SMe1EC2 and atorvastatin had a significant effect on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol) and atorvastatin had a significant effect on triacylglycerols (TGs). SMe1EC2 improved the long-term potentiation (LTP) course in the hippocampus

Hippocampal electrophysiological responses and changes in oxidative stress marker and serum lipid profile to pharmacological and non-pharmacological treatments of high-fat-fructose diet induced metabolic syndrome

The aim of our study was to evaluate the possibility of influencing the risk factors of metabolic syndrome (MetS) and metabolic cognitive syndrome. As a model of MetS, we used high-fat-fructose diet (HFFD) fed hypertriacylglycerolemic (HTG) rats. Control group included HTG rats fed with HFFD during 8 weeks (HFFD8). Furthermore, we tested the effect of pharmacological and non-pharmacological therapies. Non-pharmacological therapy, which we chose, was a change in diet from HFFD (5 weeks) to standard one (3 weeks) and thus caloric restriction (HFFD5+3). The drug we used was rosmarinic acid (RA; 100mg/kg), which we administered to rats after 5 weeks of HFFD once a day for consecutive 3 weeks with current change in diet to standard one (HFFD5+3+RA) or during lasting last 3 weeks of HFFD (HFFD8+RA). After 8 weeks of experiment, lipid peroxidation markers, lipid profile of blood serum, and neuronal transmission and synaptic plasticity (long-term potentiation [LTP]) in hippocampal sections were evaluated in vitro. We observed a significant effect of dietary change in lipid profile (decreased total cholesterol and low-density lipoprotein cholesterol [LDL-cholesterol] and increased high-density lipoprotein cholesterol [HDL-cholesterol]). The combination of pharmacological and non-pharmacological treatments caused a decrease in total cholesterol, LDL-cholesterol, and lipid peroxidation in blood serum. Change in HFFD to standard diet without treatment resulted in slight improvement in neuronal transmission in the hippocampus and caloric restriction alone also had positive effect on LTP maintenance. Our results suggest that combination of pharmacological and non-pharmacological approaches had better impact on the biochemical parameters of MetS in blood serum, but weak impact on neuronal functions in the hippocampus, where the expected positive effect was achieved only by caloric restriction