Methylene blue alleviates endothelial dysfunction and reduces oxidative stress in aortas from diabetic rats

2018 ◽  
Vol 96 (10) ◽  
pp. 1012-1016 ◽  
Author(s):  
Andreea I. Privistirescu ◽  
Alexandra Sima ◽  
Oana M. Duicu ◽  
Romulus Timar ◽  
Mariana G. Roșca ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methylene Blue ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Xylenol Orange ◽  
Diabetic Rat ◽  
Ros Production ◽  
Protective Effects

Endothelial dysfunction and the related increase in reactive oxygen species (ROS) production are important events in the pathophysiology of diabetes mellitus (DM). Methylene blue (MB) has been systematically investigated for its protective effects against refractory hypotension and mitochondrial dysfunction. We have previously demonstrated that MB improved mitochondrial respiration and partially decreased oxidative stress in diabetic rat hearts. The present study was aimed to investigate whether MB modulates vascular function and ROS production in thoracic aortic rings isolated from rats with streptozotocin-induced DM (after 4 weeks of hyperglycemia). The effects of MB (0.1 μM, 30 min ex vivo incubation) on vascular reactivity in organ chamber (phenylephrine-induced contraction, acetylcholine-induced relaxation) and H2O2production (assessed by ferrous iron xylenol orange oxidation assay) were investigated in vascular preparations with intact endothelium and after denudation. DM elicited a significant alteration of vascular function: increased contractility to phenylephrine, attenuation of acetylcholine-dependent relaxation, and augmented H2O2generation. Ex vivo incubation with MB partially reversed all these changes (by approximately 70%) in vascular segments with intact endothelial layer (but not in denuded vessels). In conclusion, MB might be useful in alleviating endothelial dysfunction and mitigating endothelial oxidative stress, observations that clearly require further investigation in the setting of cardiometabolic disease.

scholarly journals Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine ThiolactoneIn Vivovia Suppression of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Sod Activity ◽  
Homocysteine Thiolactone ◽  
Beneficial Effects ◽  
Umbilical Vein Endothelial Cells

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.

Effects of empagliflozin on oxidative stress and endothelial dysfunction in STZ-induced Type 1 diabetic rat

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
M Oelze ◽  
S Kröller-Schön ◽  
M Mader ◽  
E Zinßius ◽  
P Stamm ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Diabetic Rat

scholarly journals Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4210
Author(s):  
Yan Zhou ◽  
Chunxiu Zhou ◽  
Xutao Zhang ◽  
Chi Teng Vong ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Vascular Function ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Diabetic Mice ◽  
And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

scholarly journals Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Theresa Chikopela ◽  
Douglas C. Heimburger ◽  
Longa Kaluba ◽  
Pharaoh Hamambulu ◽  
Newton Simfukwe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Body Mass ◽  
Vascular Function ◽  
Aortic Ring ◽  
Normal Weight ◽  
Oxide Synthase ◽  
Weight Groups

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

scholarly journals An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

2020 ◽  
Vol 45 (4) ◽  
pp. 397-404
Author(s):  
Tugba Gurpinar Çavuşoğlu ◽  
Ertan Darıverenli ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Cevval Ulman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Insulin Levels ◽  
Type 2 Diabetic

AbstractObjectivesType 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats.MethodsA type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated.ResultsBoth doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels.ConclusionsBuspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

scholarly journals Differential involvement of COX1 and COX2 in the vasculopathy associated with the α-galactosidase A-knockout mouse

2009 ◽  
Vol 296 (4) ◽  
pp. H1133-H1140 ◽  
Author(s):  
James L. Park ◽  
Liming Shu ◽  
James A. Shayman
Keyword(s):  
Endothelial Dysfunction ◽  
Fabry Disease ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Knockout Mouse ◽  
Vascular Reactivity ◽  
Lysosomal Storage ◽  
Wild Type ◽  
Cox Inhibitors ◽  
Differential Involvement

The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal α-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium. Endothelial dysfunction is associated with Fabry disease and excessive cellular Gb3. We previously demonstrated that excessive vascular Gb3 in a mouse model of Fabry disease, the Gla-knockout ( Gla−/0) mouse, results in abnormal vascular function, which includes abnormal endothelium-dependent contractions, a vascular phenomenon known to involve cyclooxygenase (COX). Therefore, we hypothesized that the vasculopathy in the Gla knockout mouse may be due to a vasoactive COX-derived product. To test this hypothesis, vascular reactivity experiments were performed in aortic rings from wild-type ( Gla+/0) and Gla−/0 mice in the presence and absence of specific and nonspecific COX inhibitors. Specific inhibition of COX1 or COX2 in endothelium-intact rings from Gla−/0 mice decreased overall phenylephrine contractility compared with untreated Gla−/0 rings, whereas COX inhibitors had no effect on contractility in endothelium-denuded rings. Nonspecific inhibition of COX with indomethacin (10 μmol/l) or COX1 inhibition with valeryl salicylate (3 mmol/l) improved endothelial function in rings from Gla−/0 mice, but COX2 inhibition with NS-398 (1 μmol/l) further increased endothelial dysfunction in rings from Gla−/0 mice. These results suggest that, in the Gla−/0 mice, COX1 and COX2 activity are increased and localized in the endothelium, producing vasopressor and vasorelaxant products, which contribute to the Fabry-related vasculopathy.

Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes

2015 ◽  
Vol 93 (7) ◽  
pp. 555-561 ◽  
Author(s):  
Adrian Sturza ◽  
Oana M. Duicu ◽  
Adrian Vaduva ◽  
Maria D. Dănilă ◽  
Lavinia Noveanu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Rat Model ◽  
Experimental Diabetes ◽  
Xylenol Orange ◽  
Diabetic Rat ◽  
Organ Bath ◽  
Monoamine Oxidases ◽  
Mao B ◽  
Cardiovascular Morbidity And Mortality ◽  
Endothelium Dependent Relaxation

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.

Abstract 352: Real-time Intravital Optical Imaging Reflects the Dynamic Changes of Oxidative Stress Induced by Cigarette Smoking in Vasculatures

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ji Bak Kim ◽  
Jiheun Ryu ◽  
Joon Woo Song ◽  
Dong Joo Oh ◽  
DaeGab Gweon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoking ◽  
Optical Imaging ◽  
Real Time ◽  
Treated Group ◽  
Fluorescence Signal ◽  
Ros Production ◽  
Protective Effects ◽  
Dynamic Changes

Background: Reactive oxygen species (ROS) play a central role in cigarette smoking-induced atherogenesis. The present study aims to assess the smoking-induced acute oxidative stress within vasculatures, and evaluates whether the resveratrol, a natural polyphenol antioxidant, can counteract this ROS production, using a customized, high resolution intravital optical imaging in real-time. Methods and Results: 20-week-old male C57BL/6 mice were divided into four groups according to the preceding administration of resveratrol (R) (25mg/kg via gavage, for 7 days) and exposure to cigarette smoke (CS). To in vivo assess acute oxidative stress in blood vessels, dihydroethidium, which forms a red fluorescence (ethidium, excitation/emission: 520nm/610nm) upon reaction with ROS, was injected intraperitoneally. During CS exposure, temporal changes of fluorescence signals from the mouse cremaster muscle including vasculatures were assessed by intravital optical imaging for 15 minutes. Fluorescence signals were much more pronounced in CS exposed mice than controls (p<0.001). Resveratrol p.o. significantly reduced the CS-induced ROS signals compared to the non-treated group (fluorescence signal to noise ratio, SNR, 2.51±0.09 vs. 12.52±2.116, p=0.0002) (Figure A). Without CS exposure, fluorescence signals in targeted vasculatures were very low showing no difference between groups (SNR, 1.65±0.19 vs. 1.53±0.07, p=0.80) (Figure A). Lipid peroxidation was increased in CS group and significantly attenuated in resveratrol-treated mice (Figure B). Fluorescence microscopy and immunostainings corroborated the in vivo findings. Conclusions: The intravital optical imaging was able to in vivo estimate the dynamic changes of ROS production by CS exposure. Our data demonstrated that even a brief exposure to CS increased oxidative stress in vasculatures promptly, and the resveratrol exerts protective effects against the CS-induced acute oxidative stress.

scholarly journals Vitamin D alleviates oxidative stress in adipose tissue and mesenteric vessels from obese patients with subclinical inflammation

2020 ◽  
Vol 98 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Mihaela Ionica ◽  
Oana M. Aburel ◽  
Adrian Vaduva ◽  
Alexandra Petrus ◽  
Sonia Rațiu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Adipose Tissue ◽  
Vascular Function ◽  
Ex Vivo ◽  
Active Form ◽  
Reactive Oxygen Species Generation ◽  
Obese Patients ◽  
Tissue Samples

Obesity is an age-independent, lifestyle-triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The purpose of the present study was to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed on patients referred for general surgery (n = 30) that were randomized into two subgroups: nonobese and obese. Serum levels of C-reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D: 1,25(OH)2D3 (100 nmol/L, 12 h). The main findings are that in obese patients, (i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and (ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also improved the vascular function. We report here that the serum level of vitamin D is inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress.

scholarly journals Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress

2019 ◽  
Vol 8 (6) ◽  
pp. 918-927 ◽  
Author(s):  
Li Pang ◽  
Ping Deng ◽  
Yi-dan Liang ◽  
Jing-yu Qian ◽  
Li-Chuan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lipoic Acid ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Migration Ability ◽  
Microvascular Endothelial

Abstract Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

Sign in / Sign up

Export Citation Format

Share Document