Vitamin E-Stoffwechsel der Lunge

Vitamin E Metabolism of the Lung . Experimental and clinical data have provided evidence for the involvement of oxygen free radicals in the development of acute and chronic lung diseases. Alveolar surfactant is the prime target of oxidative air pollutants. Lung surfactant consists to 90% of lipids and contains vitamin E as most important lipophilic antioxidant. Recently, we showed that alveolar surfactant is supplemented with vitamin E during its synthesis in type II pneumocytes. Hyperoxia is very often a necessary therapeutic intervention which seems to impose oxidative stress on lung tissue. Hyperoxia caused an increase in vitamin E turnover, measured in type II pneumocytes, lamellar bodies and lung lavages. In contrast, the turnover of surfactant cholesterol and surfactant lipids does not change. Hyperoxia caused an increase in vitamin E uptake by type II pneumocytes an enrichment of vitamin E in lamellar bodies.     

Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic wistar-kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.     

Oxidative Stress as an Underlying Contributor in the Development of Chronic Complications in Diabetes Mellitus

The high prevalence of diabetes mellitus and its increasing incidence worldwide, coupled with several complications observed in its carriers, have become a public health issue of great relevance. Chronic hyperglycemia is the main feature of such a disease, being considered the responsible for the establishment of micro and macrovascular complications observed in diabetes. Several efforts have been directed in order to better comprehend the pathophysiological mechanisms involved in the course of this endocrine disease. Recently, numerous authors have suggested that excess generation of highly reactive oxygen and nitrogen species is a key component in the development of complications invoked by hyperglycemia. Overproduction and/or insufficient removal of these reactive species result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids, leading different research groups to search for biomarkers which would be capable of a proper and accurate measurement of the oxidative stress (OS) in diabetic patients, especially in the presence of chronic complications. In the face of this scenario, the present review briefly addresses the role of hyperglycemia in OS, considering basic mechanisms and their effects in diabetes mellitus, describes some of the more commonly used biomarkers of oxidative/nitrosative damage and includes selected examples of studies which evaluated OS biomarkers in patients with diabetes, pointing to the relevance of such biological components in general oxidative stress status of diabetes mellitus carriers.     

Management of Diabetes Mellitus: Could Simultaneous Targeting of Hyperglycemia and Oxidative Stress Be a Better Panacea?

The primary aim of the current management of diabetes mellitus is to achieve and/or maintain a glycated hemoglobin level of ≤6.5%. However, recent evidence indicates that intensive treatment of hyperglycemia is characterized by increased weight gain, severe hypoglycemia and higher mortality. Besides, evidence suggests that it is difficult to achieve and/or maintain optimal glycemic control in many diabetic patients; and that the benefits of intensively-treated hyperglycemia are restricted to microvascular complications only. In view of these adverse effects and limitations of intensive treatment of hyperglycemia in preventing diabetic complications, which is linked to oxidative stress, this commentary proposes a hypothesis that "simultaneous targeting of hyperglycemia and oxidative stress" could be more effective than "intensive treatment of hyperglycemia" in the management of diabetes mellitus.     

Antioxidant Drug Therapy Approaches for Neuroprotection in Chronic Diseases of the Retina

The molecular pathways contributing to visual signal transduction in the retina generate a high energy demand that has functional and structural consequences such as vascularization and high metabolic rates contributing to oxidative stress. Multiple signaling cascades are involved to actively regulate the redox state of the retina. Age-related processes increase the oxidative load, resulting in chronically elevated levels of oxidative stress and reactive oxygen species, which in the retina ultimately result in pathologies such as glaucoma or age-related macular degeneration, as well as the neuropathic complications of diabetes in the eye. Specifically, oxidative stress results in deleterious changes to the retina through dysregulation of its intracellular physiology, ultimately leading to neurodegenerative and potentially also vascular dysfunction. Herein we will review the evidence for oxidative stress-induced contributions to each of the three major ocular pathologies, glaucoma, age-related macular degeneration, and diabetic retinopathy. The premise for neuroprotective strategies for these ocular disorders will be discussed in the context of recent clinical and preclinical research pursuing novel therapy development approaches.     

抗氧化剂α-硫辛酸的生物合成研究进展

α-硫辛酸及其还原态二氢硫辛酸具有极强的抗氧化性,可改善葡萄糖代谢,减弱氧化应激,对糖尿病性白内障、糖尿病多发性神经病及心血管损伤等糖尿病并发症具有较好的预防和治疗作用。概述了α-硫辛酸的作用机制、生物合成途径及应用,重点综述了具有良好应用前景的生物法生产α-硫辛酸工艺。     

Effectiveness of Magnolol,a Lignan from Magnolia Bark,in Diabetes,Its Complications and Comorbidities—A Review

Diabetes mellitus is a chronic metabolic disease characterized by disturbances in carbohydrate, protein, and lipid metabolism, often accompanied by oxidative stress. Diabetes treatment is a complicated process in which, in addition to the standard pharmacological action, it is necessary to append a comprehensive approach. Introducing the aspect of non-pharmacological treatment of diabetes allows one to alleviate its many adverse complications. Therefore, it seems important to look for substances that, when included in the daily diet, can improve diabetic parameters. Magnolol, a polyphenolic compound found in magnolia bark, is known for its health-promoting activities and multidirectional beneficial effects on the body. Accordingly, the goal of this review is to systematize the available scientific literature on its beneficial effects on type 2 diabetes and its complications. Taking the above into consideration, the article collects data on the favorable effects of magnolol on parameters related to glycemia, lipid metabolism, or oxidative stress in the course of diabetes. After careful analysis of many scientific articles, it can be concluded that this lignan is a promising agent supporting the conventional therapies with antidiabetic drugs in order to manage diabetes and diabetes-related diseases.     

Protein Quality Control by the Ubiquitin Proteolytic Pathway: Roles in Resistance to Oxidative Stress and Disease

There is now consensus that the accumulation of oxidatively modified proteins is cytotoxic and causally related to several age-related diseases including the amyloid diseases and age-related cataracts. There is also general agreement that the ubiquitin proteolytic pathway (UPP) provides a quality control mechanism to limit accumulation of modified proteins. We asked if and how oxidative stress is related to the function of the ubiquitin proteolytic pathway, and vice versa, with the objective of obtaining information that can lead to the development of strategies to delay age-related “amyloid” or “protein precipitation” diseases such as cataracts and age-related macular degeneration. Elevated levels of ubiquitin conjugates were observed when human, rabbit, bovine, and rat lens, retina, liver cells or tissues were exposed to mild oxidative stress, which was created by exposure to paraquat, diamide, peroxide, light together with lipofuscin, and radiomimetic drugs. The increase in ubiquitin conjugates derived from an increase in substrates as well as by hyperactivation of E1, rather than inactivation of the proteasome. Using a novel glutathiolated substrate, γC-crystallin, we demonstrated that the UPP shows a previously unrecognized selectivity for such specifically oxidatively modified proteins. Selectivity of the pathway for other oxidatively modified proteins, specifically for protein carbonyls, was indicated in assays that employed the ubiquitin conjugation-competent, but degradation-resistant ubiquitin variant K6W-ubiquitin. These experiments showed that failure to execute ubiquitin-dependent proteolysis renders cells more susceptible to oxidative-stress-related cytotoxicity. Activity of the pathway is regulated in part by cellular redox status, specifically as affected by GSSG. Ubiquitination is enhanced when GSSG/GSH ratios are 0.02–0.15. Since there is potentiation of ubiquitination even when GSSG/GSH ratios are indistinguishable from basal levels, it appears that ubiquitination provides one of the most sensitive indicators of oxidative stress. Ubiquitination is attenuated when GSSG/GSH rises >0.2 and does not occur when GSSG/GSH ⩾ 2.9. The data indicate that inhibition of the pathway, which occurs upon aging, is associated with accumulation rather than the timely degradation of ubiquitin conjugates. They further suggest that if the system fails to keep up with production of substrates, high mass ubiquitin conjugates may accumulate and precipitate in cytotoxic aggregates such as are seen in many age-related syndromes, including lens cataracts or in lipofuscin and drusen in the aging retina.     

Dynamics of antioxidant action of vitamin E

Vitamin E is the major lipophilic, radical-scavenging antioxidant in vivo and protects humans from the oxidative stress mediated by active oxygen and nitrogen species. The mechanisms of the inhibition of oxidation by vitamin E in vitro are now fairly well understood, but the dynamics of antioxidant action of vitamin E in vivo have not been well elucidated yet, primarily because of the inherent heterogeneity of biological systems. In this Account, the factors which determine the antioxidant capacity of vitamin E are discussed, and the importance of its localization and mobility in the membranes and lipoproteins is emphasized.     

Oxidation resistance and abrasive wear resistance of vitamin E stabilized radiation crosslinked ultra‐high molecular weight polyethylene

The effect of gamma radiation on the oxidation and wear resistance of ultra‐high molecular weight polyethylene (UHMWPE) has been extensively studied since these properties are critical for the longevity of UHMWPE components of total joint replacement prostheses. While gamma radiation increases wear resistance of UHMWPE, the free radical generated in the lamellar regions by radiation must be stabilized before oxidative degradation occurs as the polymer ages. Initially, post‐radiation melting conducted to quench free radicals but this treatment also decreases its mechanical properties. Recently, it has been replaced by incorporation of Vitamin E into UHMWPE to combat oxidative degradation. In this study, we assessed wear resistance of Vitamin E stabilized UHMWPE under abrasive wear conditions and oxidation resistance by shelf‐aging irradiated components for 2 years. Equilibrium swelling experiments showed that Vitamin E decreased crosslink density, which affected wear resistance, but oxidation resistance was better preserved with increasing concentration of Vitamin E. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44125.     

Thermal and dynamic mechanical properties of vitamin E infused and blended ultra‐high molecular weight polyethylenes

Vitamin E (or α‐tocopherol) is an alternative via to thermal treatments to achieve oxidative stability of gamma or electron beam irradiated ultra‐high molecular weight polyethylenes (UHMWPE) used in total joint replacements. Our aim was to study the effects of vitamin E on the molecular dynamics and microstructural properties of UHMWPE. We hypothesized that the antioxidant would plasticize UHMWPE. Vitamin E was incorporated into UHMWPE at different concentrations by diffusion and blending and detected by ultraviolet and infrared spectroscopies from 500 ppm and 4000 ppm, respectively. Dynamic mechanical thermal analysis was used to characterize the influence of this antioxidant in the relaxations of the raw material. Differential scanning calorimetry and transmission electron microscopy served to characterize thermal and microstructure properties, respectively. Vitamin E concentrations above 3% by weight significantly reduced the degree of crystallinity and increased the melting transition temperature of raw UHMWPE. The presence of increasing concentrations of α‐tocopherol introduced and/or strengthened the beta relaxation, which was also shifted toward gradually lower temperatures and had rising activation energies up to 188 kJ/mol. In addition, the gamma relaxation remained unaltered on vitamin E addition. Therefore, no plasticizing effects of vitamin E on the molecular dynamics of UHMWPE could be confirmed from mechanical spectroscopy data. However, the α relaxation was modified in intensity and location due to the changes in the degree of crystallinity introduced by the incorporation of vitamin E. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats

Aim  

Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD). Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention.     

What is the role of “pressure” in the use of capillary and slit flows to determine the shear‐rate dependent viscosity of a viscoelastic fluid?

The purpose of this review article is to clear the confusion created by some investigators, who erroneously thought that the pressure transducers mounted on the wall of a capillary or slit die measured a quantity that could meaningfully be called “pressure,” accurately stated “indeterminate isotropic contribution to the total stress,” and then reported on the effect of “pressure” on the shear‐rate dependent viscosity of a viscoelastic fluid. On the other hand, reference to such a quantity is not needed to calculate the wall shear stress and thus shear viscosity in fully developed flow of incompressible, viscoelastic polymer melts in a capillary or slit die; instead only information on the gradient of the total wall normal stress is needed. Further, it is pointed out that much of the literature discussing “pressure shift factor” to describe the effect of “pressure” on the viscosity of polymer melts in flow through a capillary or slit die is based on an erroneous belief that there exists a physically meaningful isotropic “pressure” that can be measured. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers.     

Glucose Variability: How Does It Work?

A growing body of evidence points to the role of glucose variability (GV) in the development of the microvascular and macrovascular complications of diabetes. In this review, we summarize data on GV-induced biochemical, cellular and molecular events involved in the pathogenesis of diabetic complications. Current data indicate that the deteriorating effect of GV on target organs can be realized through oxidative stress, glycation, chronic low-grade inflammation, endothelial dysfunction, platelet activation, impaired angiogenesis and renal fibrosis. The effects of GV on oxidative stress, inflammation, endothelial dysfunction and hypercoagulability could be aggravated by hypoglycemia, associated with high GV. Oscillating hyperglycemia contributes to beta cell dysfunction, which leads to a further increase in GV and completes the vicious circle. In cells, the GV-induced cytotoxic effect includes mitochondrial dysfunction, endoplasmic reticulum stress and disturbances in autophagic flux, which are accompanied by reduced viability, activation of apoptosis and abnormalities in cell proliferation. These effects are realized through the up- and down-regulation of a large number of genes and the activity of signaling pathways such as PI3K/Akt, NF-κB, MAPK (ERK), JNK and TGF-β/Smad. Epigenetic modifications mediate the postponed effects of glucose fluctuations. The multiple deteriorative effects of GV provide further support for considering it as a therapeutic target in diabetes.     

Oxidative Stress in Obesity: A Critical Component in Human Diseases

Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.     

Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells

The N-acetylaspartate network begins in neurons with N-acetylaspartate production catalyzed by aspartate N-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in N-acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the N-acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25–75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/Nat8l mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the N-acetylaspartate network. This study shows that reduced N-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger N-acetylaspartate network fragility. To reveal why N-acetylaspartate is reduced in this pathology, other processes should be considered.     

Oxidative Stress in Diabetes: Implications for Vascular and Other Complications

In recent decades, oxidative stress has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence shows that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on these studies, an emerging concept is that oxidative stress is the “final common pathway” through which the risk factors for several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell–cell homeostasis; in particular, oxidative stress plays a key role in the pathogenesis of insulin resistance and β-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes and its vascular complications, the leading cause of death in diabetic patients.     

Diabetic Cardiovascular Disease Induced by Oxidative Stress

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.     

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.     

Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats

Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys.