scholarly journals Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Eleftheria Papachristoforou ◽  
Vaia Lambadiari ◽  
Eirini Maratou ◽  
Konstantinos Makrilakis
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Diabetic Complications ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vascular Complications ◽  
Glucose Variability ◽  
Ros Production ◽  
Obstructive Sleep ◽  
Antioxidant Defense Systems

Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.

scholarly journals Cabbage (Brassica oleracea var. capitata) Protects against H2O2-Induced Oxidative Stress by Preventing Mitochondrial Dysfunction in H9c2 Cardiomyoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Kwon Yang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Ros Production ◽  
Hepatic Diseases ◽  
Mitochondrial Functions ◽  
Wide Range ◽  
H9c2 Cardiomyoblasts ◽  
Cabbage Extract

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart.

scholarly journals Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

2017 ◽  
Vol 44 (3) ◽  
pp. 1174-1187 ◽  
Author(s):  
Artur Rozentsvit ◽  
Kevin Vinokur ◽  
Sherin Samuel ◽  
Ying Li ◽  
A. Martin Gerdes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Protective Effect ◽  
High Glucose ◽  
Ellagic Acid ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Vascular Complications ◽  
Ros Production ◽  
Gene And Protein Expression

Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular Compartments

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Samarjit Das ◽  
Mark J Kohr ◽  
Brittany Dunkerly ◽  
Djahida Bedja ◽  
Oliver A Kent ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Health ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Mitochondrial Gene ◽  
Cardiac Injury ◽  
Ros Production ◽  
Rna Molecules ◽  
Intracellular Compartments

Recent reports suggest that mi(cro)RNAs, non-coding RNAs, can regulate numerous human genes. miRNAs play an important role in physiologic and pathologic processes of cardiovascular health. We identified a nuclear encoded miRNA (miR-181c) that translocates into mitochondria to regulate a mitochondrial gene, and ultimately affects mitochondrial function. To investigate how miR-181c leads to cardiac injury, we designed miR-181-sponges, RNA molecules with ten repeated complimentary miR-181 “seed” sequences, and generated a set of stable-H9c2 cells by transfecting either a scrambled- or the miR-181-sponge-sequences. Sponge-H9c2 showed a significant decrease in ROS production and reduced basal mitochondrial respiration, and significant protection against Doxorubicin-induced oxidative stress. However, chronic down-regulation of the entire miR-181 family also stimulates PTEN expression, and thus the sponge decreased PI3K signaling. Thus, protection against Doxorubicin is enhanced when we treated sponge-H9c2 with siRNA against PTEN. We hypothesize that miR-181a/b targets PTEN in the cytosol and miR-181c targets mt-COX1 in the mitochondria. To extend this finding, miR-181a/b-/- and miR-181c/d-/- mice were used. miR-181a/b-/- shows a significant decrease in cardiac function at baseline compared to both miR-181c/d-/- and WT groups. Basal mitochondrial ROS production was significantly decreased in miR-181c/d-/- compare to WT or miR-181a/b-/-. Using both Electron Microscopy and light-scattering at 540 nm by isolated heart mitochondria, we found that the mitochondria are smaller in the miR-181c/d-/- , and genomic DNA-qPCR showed the number of mitochondria was markedly higher in the miR-181c/d-/- heart compared to the WT or 181a/b-/- groups. miR-181c/d-/- showed a significant decrease, while miR-181a/b-/- showed a significant increase in infarct size compared to WT, when the hearts were challenged with ischemia-reperfusion injury. Taken together, the miR-181 family regulates important signaling pathways in oxidative stress, notably with detrimental results by targeting mt-COX1 (miR-181c), or with protection by targeting PTEN (miR-181a/b).

Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice

2007 ◽  
Vol 102 (5) ◽  
pp. 1806-1814 ◽  
Author(s):  
Ah-Mee Park ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O2 and 2 min 21% O2) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H2O2 scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.

scholarly journals Targeting Dynamin 2 as a Novel Pathway to Inhibit Cardiomyocyte Apoptosis Following Oxidative Stress

2016 ◽  
Vol 39 (6) ◽  
pp. 2121-2134 ◽  
Author(s):  
Danchen Gao ◽  
Jian Yang ◽  
Yutao Wu ◽  
Qiwen Wang ◽  
Qiaoling Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Protective Effects ◽  
Mitochondrial Fragmentation ◽  
Induced Apoptosis ◽  
Dynamin 2

Background/Aims: Inhibition of Drp-1-mediated mitochondrial fission limits reactive oxygen species (ROS) production and apoptosis in cardiomyocytes subjected to ischemia/reperfusion injury. It remains unknown if Dynamin 2 inhibition results in similar protective effects. Here we studied the role of Dynamin 2 in cardiomyocyte oxidative stress-induced apoptosis and ROS production. Methods: The effect of lentiviral shRNA (lv5-shRNA) mediated Dynamin 2 knockdown on apopotosis, mitochondria, and ROS production were studied in neonatal mouse cardiomycytes, which were further treated with either selective Drp1 inhibitor mdivi-1 or the Dynamin 2/Drp1 inhibitor Dynasore. Apoptosis was evaluated by flow cytometry. Mitochondrial morphology and transmembrane potential (ΔΨm) were studied by confocal microscopy, and ROS production was detected by dichlorofluorescein diacetate. Results: Inhibition of Drp1 and Dynamin 2 protected against mitochondrial fragmentation, maintained ΔΨm, attenuated cellular ROS production and limited apoptosis. Moreover, Lv5-shRNA mediated knockdown of Dynamin 2 alleviated mitochondrial fragmentation, and reduced both ROS production and oxidative stress-induced apoptosis. The protective effects of Dynamin 2 knockdown were enhanced by Dynasore, indicating an added benefit. Conclusions: Oxidative stress-induced apoptosis and ROS production are attenuated by not only Drp1 inhibition but also Dynamin 2 inhibition, implicating Dynamin 2 as a mediator of oxidative stress in cardiomyocytes.

scholarly journals Biomarkers of Oxidative Stress and Endothelial Dysfunction After Tourniquet Release in Children

2011 ◽  
pp. S137-S145
Author(s):  
I. BUDIC ◽  
D. PAVLOVIC ◽  
G. KOCIC ◽  
T. CVETKOVIC ◽  
D. SIMIC ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Regional Anesthesia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Venous Blood ◽  
Total Intravenous Anesthesia ◽  
Inhalational Anesthesia ◽  
Intravenous Anesthesia ◽  
Tourniquet Release

Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field and facilitate dissection. This prospective study was carried out to examine possible effect of different anesthesia techniques on oxidative stress and endothelial dysfunction connected with ischemia-reperfusion injury during extremity operations at children's age. Patients were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples for determination of the malondialdehyde in plasma and erythrocytes, protein carbonyl groups concentration as well as plasma nitrites and nitrates level and xanthine oxidase activity were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release, 5 and 20 min after tourniquet release. This study demonstrates that total intravenous anesthesia with propofol and regional anesthesia techniques provide better antioxidant defense and reduce endothelial dysfunction than general inhalational anesthesia with sevoflurane during tourniquet application in pediatric extremity surgery.

Abstract P226: Endothelin-1 Overexpression Exaggerates Diabetes-induced Endothelial Dysfunction by Altering Oxidative Stress

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sofiane Ouerd ◽  
Noureddine Idris-Khodja ◽  
Muhammad O Mian ◽  
Jordan Gornitsky ◽  
Tlili Barhoumi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Mrna Expression ◽  
Vascular Complications ◽  
Mesenteric Arteries ◽  
Ros Production ◽  
Reverse Transcription Quantitative Pcr ◽  
Patients With Diabetes ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Objective: Increased endothelin (ET)-1 expression has been shown to cause endothelial dysfunction and oxidative stress. Plasma ET-1 is increased in patients with diabetes mellitus. Since endothelial dysfunction often precedes vascular complications in diabetes, we sought to determine whether ET-1 contributes to diabetes-induced endothelial dysfunction. We hypothesized that overexpression of ET-1 in the endothelium will exaggerate diabetes-induced endothelial dysfunction. Methods: Diabetes was induced by streptozotocin IP injections (STZ, 55 mg/kg/day) for 5 days in 6-week-old male wild-type (WT) mice and in mice overexpressing human ET-1 restricted to the endothelium (eET-1). Mice were studied 14 weeks later. Endothelial function and vascular remodeling using pressurized myography, reactive oxygen species (ROS) production by dihydroethidium staining and mRNA expression by reverse transcription-quantitative PCR were assessed in mesenteric arteries (MA). Results: MA endothelium-dependent vasodilatory responses to acetylcholine were reduced 24% by diabetes in WT (E max : 61±6 vs 84±3%, P <0.05), and further decreased by 12% in eET-1 (E max : 49±5, P <0.05). Diabetes decreased MA media/lumen in WT (2.4±0.1% vs 3.3±0.2%, P <0.05) and eET-1 (2.9±0.2% vs 4.0±0.2%, P <0.05), whereas ET-1 overexpression increased MA media/lumen to a similar extent in diabetic and non-diabetic WT mice ( P <0.05). Vascular ROS production in MA was increased 2-fold by diabetes in WT (5.0±0.5 vs 2.5±0.3 relative fluorescence units [RFU]/μm 2 , P <0.05) and further augmented 1.7-fold in eET-1 (8.5±1.2 RFU/μm 2 , P <0.05). Diabetes reduced endothelial nitric oxide synthase (eNOS, Nos3) mRNA expression in eET-1 by 50% (0.7±0.1 vs 1.4±0.2, P <0.05) but not in WT. Induction of diabetes caused a 50% increase in superoxide dismutase 1 ( Sod1 , 1.5±0.2 vs 1.0±0.0, P <0.05) and a 30% increase in Sod2 (1.3±0.1 vs 1.0±0.0, P <0.05) mRNA expression in WT but not in eET-1. Conclusions: Increased expression of ET-1 exaggerates diabetes-induced endothelial dysfunction. This may be caused by an increase in vascular oxidative stress, a decrease in eNOS expression and a decrease in antioxidant capacity.

scholarly journals CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via Activating Sirt3/FOXO3 Pathway

2018 ◽  
Vol 48 (6) ◽  
pp. 2350-2363 ◽  
Author(s):  
Ling-Fang Wang ◽  
Cong-Cong Huang ◽  
Yun-Fei Xiao ◽  
Xiao-Hui Guan ◽  
Xiao-Nv Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cell ◽  
Ros Production ◽  
High Fat ◽  
Sod Activity ◽  
Heart Injury

Background/Aims: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. Methods: The metabolites in heart from wild type (WT) and CD38 knockout (CD38-/-) mice were examined using metabolomics analysis. Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD) activity, reactive oxygen species (ROS) production, triglyceride concentration and gene expression were examined by biochemical analysis and QPCR. Results: Our results revealed that CD38 deficiency significantly elevated the intracellular glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of free fatty acids and increased intracellular NAD+ level in heart from CD38-/- mice fed with HFD. In addition, in vitro knockdown of CD38 significantly attenuated OA-induced cellular injury, ROS production and lipid synthesis. Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were significantly decreased in the cells after OA stimulation. Conclusion: Our results demonstrated that CD38 deficiency protected heart from HFD-induced oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress pathway.

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