scholarly journals Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Reddemma Sandireddy ◽  
Veera Ganesh Yerra ◽  
Aparna Areti ◽  
Prashanth Komirishetty ◽  
Ashutosh Kumar
Keyword(s):  
Oxidative Stress ◽  
Diabetic Neuropathy ◽  
Nitrosative Stress ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Polyol Pathway ◽  
The Body ◽  
Nerve Tissue ◽  
Chronic Hyperglycemia ◽  
Hexosamine Pathway

In Diabetes, the chronic hyperglycemia and associated complications affecting peripheral nerves are one of the most commonly occurring microvascular complications with an overall prevalence of 50–60%. Among the vascular complications of diabetes, diabetic neuropathy is the most painful and disabling, fatal complication affecting the quality of life in patients. Several theories of etiologies surfaced down the lane, amongst which the oxidative stress mediated damage in neurons and surrounding glial cell has gained attention as one of the vital mechanisms in the pathogenesis of neuropathy. Mitochondria induced ROS and other oxidants are responsible for altering the balance between oxidants and innate antioxidant defence of the body. Oxidative-nitrosative stress not only activates the major pathways namely, polyol pathway flux, advanced glycation end products formation, activation of protein kinase C, and overactivity of the hexosamine pathway, but also initiates and amplifies neuroinflammation. The cross talk between oxidative stress and inflammation is due to the activation of NF-κB and AP-1 and inhibition of Nrf2, peroxynitrite mediate endothelial dysfunction, altered NO levels, and macrophage migration. These all culminate in the production of proinflammatory cytokines which are responsible for nerve tissue damage and debilitating neuropathies. This review focuses on the relationship between oxidative stress and neuroinflammation in the development and progression of diabetic neuropathy.

scholarly journals Dyslipidemia, Diabetes and Atherosclerosis: Role of Inflammation and ROS-Redox-Sensitive Factors

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1602
Author(s):  
Elham Hasheminasabgorji ◽  
Jay C. Jha
Keyword(s):  
Oxidative Stress ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Premature Mortality ◽  
Organ Damage ◽  
Lipid Lowering ◽  
Related Factors ◽  
Complications Of Diabetes ◽  
Chronic Hyperglycemia ◽  
And Oxidative Stress

The prevalence of diabetes is growing at an alarming rate with increased disability, morbidity, and often premature mortality because of the various complications of this disorder. Chronic hyperglycemia, dyslipidemia, and other metabolic alterations lead to the development and progression of macro- and microvascular complications of diabetes including cardiovascular, retinal and kidney disease. Despite advances in glucose and lipid lowering treatments, a large number of diabetic individuals develop one or more types of these complications, ultimately leading to end-organ damage over the time. Atherosclerosis is the major macro-vascular complications of diabetes and the primary underlying cause of cardiovascular disease (CVD) posing heavy burden on the health care system. In this review, we discuss the involvement of dyslipidemia in the progression of atherosclerosis by activating the pro-inflammatory cytokines and oxidative stress-related factors. In addition, we also provide information on various pharmacological agents that provides protection against diabetic atherosclerosis by reducing inflammation and oxidative stress.

scholarly journals Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy

2019 ◽  
Vol 20 (18) ◽  
pp. 4627 ◽  
Author(s):  
Raffaele Simeoli ◽  
Alessandra Fierabracci
Keyword(s):  
Oxidative Stress ◽  
Diabetic Neuropathy ◽  
Peripheral Nerves ◽  
Recent Literature ◽  
Polyol Pathway ◽  
Cytokine Release ◽  
Chronic Hyperglycemia ◽  
Pathway Activation ◽  
Non Coding Rnas

Diabetic neuropathy is a serious complication of chronic hyperglycemia in diabetes patients. This complication can involve both peripheral sensorimotor and autonomic nervous system. The precise nature of injury to the peripheral nerves mediated by chronic hyperglycemia is unknown; however, several mechanisms have been proposed including polyol pathway activation, enhanced glycation of proteins and lipids, increased oxidative stress, and cytokine release in the site of injury. MicroRNAs (miRNAs) are small non-coding RNAs that mediate RNA interference by post-transcriptionally modulating gene expression and protein synthesis. Therefore, they have been implicated in several developmental, physiological, and pathophysiological processes where they modulate the expression of different proteins. Recently, miRNAs gained an increasing attention also for their role as diagnostic test in many diseases due to their stability in serum and their easy detection. Furthermore, recent studies suggest that miRNAs may be involved in diabetic neuropathy although their role in the onset and the development of this complication is not fully understood. In this review, we discuss the most recent literature providing evidence for miRNAs role in diabetic neuropathy opening new pathways to improve both early diagnosis and treatment of this complication.

A Review on Cellular and Molecular Mechanisms Linked to the Development of Diabetes Complications

2020 ◽  
Vol 16 ◽  
Author(s):  
Rishabh A. Babel ◽  
Manoj P. Dandekar
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Macrovascular Complications ◽  
Physical Work ◽  
Complications Of Diabetes ◽  
Chronic Hyperglycemia ◽  
Hexosamine Pathway ◽  
Artery Disease ◽  
Microvascular And Macrovascular Complications

: Modern lifestyle, changing eating habits and reduced physical work have been known to culminate into making diabetes a global pandemic. Hyperglycemia during the course of diabetes is an important causative factor for the development of both microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, stroke and peripheral artery disease) complications. In this article, we summarize several mechanisms accountable for the development of both microvascular and macrovascular complications of diabetes. Several metabolic and cellular events are linked to the augmentation of oxidative stress like the activation of advanced glycation endproducts (AGE) pathway, polyol pathway, protein kinase C (PKC) pathway, poly-ADP ribose polymerase (PARP) and hexosamine pathway. Oxidative stress also leads to production of reactive oxygen species (ROS) like hydroxyl radical, superoxide anion and peroxides. Enhanced levels of ROS rescind the anti-oxidant defence mechanisms associated with superoxide dismutase, glutathione and ascorbic acid. Moreover, ROS triggers oxidative damages at the level of DNA, protein and lipids which eventually cause cell necrosis or apoptosis. These physiological insults may be related to the microvascular complications of diabetes by negatively impacting the eyes, kidneys and brain. While underlying pathomechanism of the macrovascular complications is quite complex, hyperglycemia associated atherosclerotic abnormalities like changes in the coagulation system, thrombin formation, fibrinolysis, platelet and endothelial function and vascular smooth muscle is well proven. Since hyperglycemia also modulates the vascular inflammation, cytokines, macrophage activation and gene expression of growth factors, elevated blood glucose level may play a central role in the development of macrovascular complications of diabetes. Taken collectively, chronic hyperglycemia and increased production of ROS are the miscreants for the development of microvascular and macrovascular complications of diabetes.

scholarly journals Male Infertility: Pathogenetic Significance of Oxidative Stress and Antioxidant Defence (Review)

2021 ◽  
Vol 24 (6) ◽  
pp. 107-116
Author(s):  
Vsevolod Koshevoy ◽  
Svitlana Naumenko ◽  
Pavlo Skliarov ◽  
Serhiy Fedorenko ◽  
Lidia Kostyshyn
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Malonic Dialdehyde ◽  
The Body ◽  
Redox Activity ◽  
Enzymatic System ◽  
Male Body ◽  
Mitochondrial Potential

The basis of the pathogenesis of male infertility is the processes of peroxide oxidation of biological substrates, especially lipids and proteins. By destroying the sperm membrane, toxic peroxidation products reduce its motility and ability to fertilize the egg, which is determined by a decrease in the number of motile sperm in the ejaculate. These changes lead to complete or partial male infertility. The authors of the review found that is accompanied by a damaging effect on the structural and functional activity of the gonads and is manifested, in particular, by an imbalance in the hormonal background of the male body. Similar effects are characteristic of an increase in the content of reactive Nitrogen species and its metabolites, which cause nitrosative stress, which is also the cause of male hypofertility and is inseparable from the state of oxidative stress. In scientific work it is determined that the accumulation of harmful peroxidation products leads to damage and destruction of sperm DNA, reduced activity of acrosomal enzymes and mitochondrial potential of sperm, reduced overall antioxidant activity. This makes it impossible for an adequate response of the body. Multi component antioxidant defense system resists stress. It is represented by enzymatic and non-enzymatic links, which can neutralize harmful radicals and peroxidation products. It contributes to the full manifestation of reproductive function. The presence of powerful antioxidant properties of catalase, superoxide dismutase, and enzymes of the thiol-disulfide system, which form the enzymatic system of antioxidant protection, as well as selenium, zinc, copper, other trace elements, retinol, tocopherol, ascorbic acid, and vitamins as parts of the non-enzymatic system is shown. The efficiency of registration is substantiated thin biochemical shift detectors or complex methods, such as total antioxidant status of sperm or sperm plasma, mitochondrial membrane potential, etc along with simple markers of oxidative stress, such as diene conjugates, malonic dialdehyde, and metabolites of the Nitrogen Oxide cycle. Given the leading role of oxidative stress in the development of male hypofertility, the prospect of further research is the search for modern means for correction, especially among substances with pronounced redox activity

scholarly journals Glycemic Variability and Vascular Complications in Patients with Type 2 Diabetes Mellitus

Folia Medica ◽  
2017 ◽  
Vol 59 (3) ◽  
pp. 270-278 ◽  
Author(s):  
Martin Caprnda ◽  
Dasa Mesarosova ◽  
Pablo Fabuel Ortega ◽  
Boris Krahulec ◽  
Emmanuel Egom ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Glycemic Variability ◽  
Cerebral Stroke ◽  
Chronic Hyperglycemia ◽  
Type 2 Dm ◽  
Artery Disease ◽  
Index Value

AbstractBackground:Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications.Methods:99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease – CAD; peripheral artery disease – PAD; cerebral stroke – CS) and microvascular (diabetic retinopathy – DR; nephropathy – DN; peripheral neuropathy – DPPN) DM complications were done.Results:Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05).Conclusion:In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

scholarly journals ALTERATIONS OF LIPID LEVELS MAY INDUCE THE INSULIN RESISTANCE IN TYPE TWO DIABETES MELLITUS: A SYSTEMIC REVIEW

2020 ◽  
pp. 9-20
Author(s):  
DIVYA JYOTHI P ◽  
DOONDI PHANI KUMAR N ◽  
VINAY MOHAN A ◽  
RAMYA A
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Microvascular Complications ◽  
Hormone Secretion ◽  
International Diabetes Federation ◽  
The Body ◽  
Systemic Review ◽  
Cardiac Complications ◽  
Sequence Of Events ◽  
Chronic Hyperglycemia

Diabetes mellitus (DM) is not one disorder; it represents a series of metabolic conditions related to hyperglycemia and caused by defects in hormone secretion and hormone action. Exposure to chronic hyperglycemia may result in microvascular complications in the retina (diabetic retinopathy), kidney (diabetic nephropathy), neuron (diabetic-neuropathy), skin, foot, and cardiac complications (stroke, hypertension…etc.). International Diabetes Federation estimates that 1.1 million children and adolescents aged 14–19 years have type one DM. Without interventions to halt the increase in diabetes, there will be at least 629 million people living with diabetes by 2045. In the body, white adipose tissue is the leading site for the storage of excess energy produced from the food intake in large quantities, of the development of insulin resistance (IR) and type 2 DM by the over intake of fatty acid in the body. It results in the accumulation of fatty acyl co-A (FA-CoA) within the myocytes. It leads to improper signaling of the insulin and reduces the level in the myocytes and pancreases beta cells. It combines with genetically reduces the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) coactivator-1, initiates the inflammation process by the activation of the tumor necrotic factor alpha and protein kinase C. These alterations lead to further increase the intramyocellular FA-CoA and triglycerides. The sequence of events may develop mitochondrial dysfunction in the sarcolemma outer layers. Finally improves IR also with increasing intramyocellular lipids. This concept might be helpful to those who are pursuing endocrinology specialization, nursing staff, pharmacists, and other medical departments.

scholarly journals Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

2014 ◽  
Vol 306 (8) ◽  
pp. C768-C778 ◽  
Author(s):  
Abdul Q. Sheikh ◽  
Courtney Kuesel ◽  
Toloo Taghian ◽  
Jennifer R. Hurley ◽  
Wei Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Microvascular Complications ◽  
The Body ◽  
Type I ◽  
Chronic Hyperglycemia ◽  
Biomechanical Responses ◽  
Acute And Chronic Exposure

Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory by endothelial cells may play the key role in microvascular complications in diabetes, providing a potential target for therapeutic approaches. This study tested the hypothesis that a proangiogenic environment can augment diabetes-induced deficiencies in endothelial cell angiogenic and biomechanical responses. Endothelial responses were quantified for two models of diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo chronic diabetes model where the cells were isolated from rats with type I streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide expression, cell morphology, orientation, proliferation, and apoptosis were determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel. The effects of biomechanical stimulation were assessed following cell exposure to uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium angiogenic response, with differential effects of acute and chronic exposure to high-glucose conditions, consistent with the concept that endothelial cells may have a long-term “hyperglycemic memory” of the physiological environment in the body. Furthermore, endothelial cell exposure to strain significantly diminishes their angiogenic potential following strain application. Both diabetes and strain-associated deficiencies can be augmented in the proangiogenic nanofiber microenvironment. These findings may contribute to the development of novel approaches to reverse hyperglycemic memory of endothelium and enhance vascularization of the diabetic heart, where improved angiogenic and biomechanical responses can be the key factor to successful therapy.

scholarly journals Glycemic control as an important tool in the prevention of cardiovascular aging in patients with diabetes mellitus

2021 ◽  
pp. 238-244
Author(s):  
O. A. Shatskaya ◽  
I. Z. Bondarenko ◽  
S. S. Kukharenko
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular System ◽  
Diabetes Management ◽  
Vascular Complications ◽  
The Body ◽  
Self Control ◽  
Risk Of Death ◽  
Chronic Hyperglycemia ◽  
Age Related ◽  
Patients With Diabetes

In recent decades, there has been a significant increase in the incidence and prevalence of diabetes mellitus. Diabetes mellitus is characterized by the development of vascular complications leading to early disability and a decrease in the life expectancy of patients. Aging of the body inevitably leads to the occurrence of age-related diseases, including the cardiovascular system, and increases the risk of death. Metabolic and structural and functional disorders of the cardiovascular system arising in diabetes mellitus have common pathophysiological mechanisms with aging of the body. Chronic hyperglycemia can accelerate the aging process and play a decisive role in the occurrence and prognosis of cardiovascular events in patients with diabetes mellitus. Achieving target glycemic values is an important step towards preventing vascular complications in patients with diabetes mellitus. Improved models of glucometers, equipped with a number of additional functions, allow for structured self-control of glycemia, analyze the data obtained and carry out timely correction of therapy, actively involve patients in the process of diabetes management, which will significantly increase the efficiency of disease management, reduce the risk of complications in patients and improve the quality of life.

scholarly journals Role of Protein Kinase C in Diabetic Complications

2019 ◽  
Vol 7 (2) ◽  
pp. 87-95
Author(s):  
Simran ◽  
Amarjot Kaur Grewal ◽  
Sandeep Arora ◽  
Thakur Gurjeet Singh
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Diabetic Complications ◽  
Intracellular Signaling ◽  
Microvascular Complications ◽  
Polyol Pathway ◽  
Cellular Damage ◽  
Kinase C ◽  
Hexosamine Pathway ◽  
Systemic Disorder

Diabetes is the most common and systemic disorder associated with hyperglycemia which is the significant factor in the development of micro- and macrovascular changes. Many mechanistic approaches i.e. activation of Protein kinase C, glycation end products production, hexosamine pathway and polyol pathway induce cellular damage and lead to the development of diabetic complications like nephropathy, neuropathy, retinopathy, and myopathy. One of the adverse effects of long-lasting hyperglycemia is activation of PKC (intracellular signaling enzyme) and has become a field of great research interest. Hence, in this review special emphasis is placed on microvascular complications which are due to activation of PKC. Clinical trials have also been conducted using selective PKC inhibitors and have shown positive results against hyperglycemia.

scholarly journals Cross-Talk between Mitochondrial Dysfunction-Provoked Oxidative Stress and Aberrant Noncoding RNA Expression in the Pathogenesis and Pathophysiology of SLE

2019 ◽  
Vol 20 (20) ◽  
pp. 5183 ◽  
Author(s):  
Chang-Youh Tsai ◽  
Song-Chou Hsieh ◽  
Cheng-Shiun Lu ◽  
Tsai-Hung Wu ◽  
Hsien-Tzung Liao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cross Talk ◽  
Noncoding Rna ◽  
Nitrosative Stress ◽  
Noncoding Rnas ◽  
The Body ◽  
Rna Expression ◽  
Epigenetic Regulations ◽  
The Cross

Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease involving almost every organ. Polygenic predisposition and complicated epigenetic regulations are the upstream factors to elicit its development. Mitochondrial dysfunction-provoked oxidative stress may also play a crucial role in it. Classical epigenetic regulations of gene expression may include DNA methylation/acetylation and histone modification. Recent investigations have revealed that intracellular and extracellular (exosomal) noncoding RNAs (ncRNAs), including microRNAs (miRs), and long noncoding RNAs (lncRNAs), are the key molecules for post-transcriptional regulation of messenger (m)RNA expression. Oxidative and nitrosative stresses originating from mitochondrial dysfunctions could become the pathological biosignatures for increased cell apoptosis/necrosis, nonhyperglycemic metabolic syndrome, multiple neoantigen formation, and immune dysregulation in patients with SLE. Recently, many authors noted that the cross-talk between oxidative stress and ncRNAs can trigger and perpetuate autoimmune reactions in patients with SLE. Intracellular interactions between miR and lncRNAs as well as extracellular exosomal ncRNA communication to and fro between remote cells/tissues via plasma or other body fluids also occur in the body. The urinary exosomal ncRNAs can now represent biosignatures for lupus nephritis. Herein, we’ll briefly review and discuss the cross-talk between excessive oxidative/nitrosative stress induced by mitochondrial dysfunction in tissues/cells and ncRNAs, as well as the prospect of antioxidant therapy in patients with SLE.

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