scholarly journals Organic Nitrates and Nitrate Resistance in Diabetes: The Role of Vascular Dysfunction and Oxidative Stress with Emphasis on Antioxidant Properties of Pentaerithrityl Tetranitrate

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Matthias Oelze ◽  
Swenja Schuhmacher ◽  
Andreas Daiber

Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
M. D. Mauricio ◽  
S. Guerra-Ojeda ◽  
P. Marchio ◽  
S. L. Valles ◽  
M. Aldasoro ◽  
...  

Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Alessandra Magenta ◽  
Simona Greco ◽  
Maurizio C. Capogrossi ◽  
Carlo Gaetano ◽  
Fabio Martelli

Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production,p66Shcprotein.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Paolo Severino ◽  
Andrea D’Amato ◽  
Lucrezia Netti ◽  
Mariateresa Pucci ◽  
Fabio Infusino ◽  
...  

Ischemic heart disease (IHD) has several risk factors, among which diabetes mellitus represents one of the most important. In diabetic patients, the pathophysiology of myocardial ischemia remains unclear yet: some have atherosclerotic plaque which obstructs coronary blood flow, others show myocardial ischemia due to coronary microvascular dysfunction in the absence of plaques in epicardial vessels. In the cross-talk between myocardial metabolism and coronary blood flow (CBF), ion channels have a main role, and, in diabetic patients, they are involved in the pathophysiology of IHD. The exposition to the different cardiovascular risk factors and the ischemic condition determine an imbalance of the redox state, defined as oxidative stress, which shows itself with oxidant accumulation and antioxidant deficiency. In particular, several products of myocardial metabolism, belonging to oxidative stress, may influence ion channel function, altering their capacity to modulate CBF, in response to myocardial metabolism, and predisposing to myocardial ischemia. For this reason, considering the role of oxidative and ion channels in the pathophysiology of myocardial ischemia, it is allowed to consider new therapeutic perspectives in the treatment of IHD.


2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.


2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.


2019 ◽  
Vol 41 (5) ◽  
pp. 859-859
Author(s):  
Erum Shireen Erum Shireen ◽  
Wafa Binte Ali Wafa Binte Ali ◽  
Maria Masroor Maria Masroor ◽  
Saeeda Bano Saeeda Bano ◽  
Samina Iqbal Samina Iqbal ◽  
...  

Acute exposure to stress is connected to many disorders that promote the toxicity of oxygen radical generators leading to increase in the levels of enzymes and also the activation of the HPA axis. The present study uses a preclinical approach to elucidate some prospective stress-induced behavioral and biochemical effects. The aim of current study was to investigate the relationship between stress and behavioral changes after exposing animals to 2h immobilization stress. We also evaluated the concentration of corticosterone, glucose and endogenous leptin levels in unstressed and stressed animals to explore the possible role of HPA axis in the modulation of stressed induced behavioral deficits. Rats were divided into stressed and unstressed groups. Behavioral activities were monitored in open field activity and light dark transition box after the termination of 2h immobilization period. Animals were then decapitated and plasma samples were collected for catalase, SOD, corticosterone, and glucose estimation. Results showed that exposure to acute stress produced a significant decrease in the activity of rats in the novel environment (open field) and light dark transition box. On the other hand, concomitant elevated level of peripheral markers of oxidative stress such as oxidative enzymes, corticosterone and endogenous leptin were also observed. Therefore, current study seems to suggest an important role of compounds having antioxidant properties for the treatment of stress and related disorders.


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