Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

2020 ◽  
Vol 21 (3) ◽  
pp. 143-149
Author(s):  
I. A. Chernov ◽  
◽  
Yu. A. Kirillov ◽  
D. A. Areshidze ◽  
M. A. Kozlova ◽  
...  

The review focuses on the pathogenetic mechanisms of ethanol influence on the development of oxidative stress (OS) and endothelial dysfunction (ED). It is shown that both in acute and chronic alcohol intoxication, the intake of ethanol in the body initiates the development of OS, the formation of reactive oxygen species, causes a decrease in the content of endothelium-derived relaxing factors (nitric oxide (NO), prostacyclin, endothelium-derived hyperpolarization factor (EDHF)), an increase in the concentration of endothelium-derived constricting factors (endothelin, angiotensin-II), thereby causing the development of ED. When alcohol is consumed in small doses by healthy non-drinkers, ethanol can act as an antioxidant, cause the neutralization of reactive oxygen species, promote the formation of NO, and prevent the formation of ED. Currently used methods for evaluating ED allow us to characterize the functional state of the endothelium. Structural changes in the blood vessel wall as a manifestation of ED in alcoholic disease are not sufficiently described, which indicates the need to study them using modern histological, histochemical, immunohistochemical and electron microscopic methods.


Author(s):  
Ahmed Karoui ◽  
Clément Crochemore ◽  
Najah Harouki ◽  
Cécile Corbière ◽  
David Preterre ◽  
...  

Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular (CV) diseases. In a previous experimental study, we showed that diesel exhaust (DE) exposures induced cardiac mitochondrial and CV dysfunctions associated with the gaseous phase. Here, we hypothesized that NO2 exposures to levels close to those found in DE induce a mitochondrial reactive oxygen species (ROS) production, which contribute to an endothelial dysfunction, an early indicator for numerous CV diseases. For this, we studied the effects of NO2 on ROS production and its impacts on the mitochondrial, coronary endothelial and cardiac functions, after acute (one single exposure) and repeated (three h/day, five days/week for three weeks) exposures in Wistar rats. Acute NO2 exposure induced an early but reversible mitochondrial ROS production. This event was isolated since neither mitochondrial function nor endothelial function were impaired, whereas cardiac function assessment showed a reversible left ventricular dysfunction. Conversely, after three weeks of exposure this alteration was accompanied by a cardiac mitochondrial dysfunction highlighted by an alteration of adenosine triphosphate (ATP) synthesis and oxidative phosphorylation and an increase in mitochondrial ROS production. Moreover, repeated NO2 exposures promoted endothelial dysfunction of the coronary arteries, as shown by reduced acetylcholine-induced vasodilatation, which was due, at least partially, to a superoxide-dependent decrease of nitric oxide (NO) bioavailability. This study shows that NO2 exposures impair cardiac mitochondrial function, which, in conjunction with coronary endothelial dysfunction, contributes to cardiac dysfunction. Together, these results clearly identify NO2 as a probable risk factor in ischemic heart diseases.


2008 ◽  
Vol 105 (5) ◽  
pp. 1632-1642 ◽  
Author(s):  
Lakshmi Santhanam ◽  
David W. Christianson ◽  
Daniel Nyhan ◽  
Dan E. Berkowitz

Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contribute to the endothelial dysfunction that underlies this vascular stiffness, independent of other age-related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate (l-arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis. Not only does this lead to impaired NO production but also it contributes to the enhanced production of reactive oxygen species by NOS. Although arginase abundance is increased in vascular aging models, it appears that posttranslational modification by S-nitrosylation of the enzyme enhances its activity as well. The S-nitrosylation is mediated by the induction of NOS2 in the endothelium. Furthermore, arginase activation contributes to aging-related vascular changes by mechanisms that are not directly related to changes in NO signaling, including polyamine-dependent vascular smooth muscle proliferation and collagen synthesis. Taken together, arginase may represent an as yet elusive target for the modification of age-related vascular and ventricular stiffness contributing to cardiovascular morbidity and mortality.


2018 ◽  
Vol 100 ◽  
pp. 1-19 ◽  
Author(s):  
Maria Angela Incalza ◽  
Rossella D'Oria ◽  
Annalisa Natalicchio ◽  
Sebastio Perrini ◽  
Luigi Laviola ◽  
...  

2013 ◽  
Vol 20 (2) ◽  
pp. 149-155
Author(s):  
Mircea Munteanu ◽  
Adrian Sturza ◽  
Adalbert Schiller ◽  
Romulus Timar

Abstract Cardiovascular disease is the leading cause of disease / mortality worldwide. It is generally accepted that increased production of reactive oxygen species (ROS) has an important role in cardiovascular pathology, contributing to endothelial dysfunction and to the aggravation of atherosclerosis. Among all cardiovascular risk factors, diabetes mellitus is one of the most important. The worldwide prevalence of diabetes has increased rapidly even in developing countries, doubling the combined risk of cardiovascular events in patients with hypertension. In diabetes, increased reactive oxygen species (ROS) production leads to endothelial dysfunction, recognized by the presence of impaired vascular relaxation, increased vascular smooth muscle cells growth and hypertrophy, all together contributing to atherosclerotic plaque formation. On this basis, the vascular endothelium has emerged as a therapeutic target, with the aim to improve systemic metabolic state by improving vascular function. In this review we have focused on the most important sources of reactive oxygen species generated by vascular endothelium in diabetic patients (NADPH Oxidases, eNOS uncoupling, Xanthine oxidase). The importance of oxidative stress in mediating the vascular complications of diabetes is supported by studies showing that antioxidant therapy correct the vascular function in humans or in experimental models of diabetes. Therefore, understanding the physiological mechanisms involved in vascular disorders resulting from hyperglycemia is essential for the proper use of available therapeutic resources.


2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.


Author(s):  
Arnab Banerjee ◽  
Debasmita Das ◽  
Rajarshi Paul ◽  
Sandipan Roy ◽  
Ankita Bhattacharjee ◽  
...  

AbstractBackgroundIn the present era, obesity is increasing rapidly, and high dietary intake of lipid could be a noteworthy risk factor for the occasion of obesity, as well as nonalcoholic fatty liver disease, which is the independent risk factor for type 2 diabetes and cardiovascular disease. For a long time, high-lipid diet (HLD) in “fast food” is turning into part of our everyday life. So, we were interested in fulfilling the paucity of studies by means of preliminary evaluation of these three alternative doses of HLD on a rat model and elucidating the possible mechanism of these effects and divulging the most alarming dose.MethodsThirty-two rats were taken, and of these, 24 were fed with HLD in three distinctive compositions of edible coconut oil and vanaspati ghee in a ratio of 2:3, 3:2 and 1:1 (n = 8), orally through gavage at a dose of 10 mL/kg body weight for a period of 28 days, whereas the other eight were selected to comprise the control group.ResultsAfter completion of the experiment, followed by analysis of data it was revealed that hyperlipidemia with increased liver and cardiac marker enzymes, are associated with hepatocellular injury and cardiac damage. The data also supported increased proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). As oxidative stress parameter increased in both liver and heart, there is also an increased in TNF-α due to an increased expression of inducible nitric oxide (NO) synthase, which led to a high production of NO. Moreover, HLD treatment explicitly weakens reasonability of hepatocytes and cardiomyocytes conceivably through G0/G1 or S stage capture or perhaps by means of enlistment of sub-G0/G1 DNA fragmentation and a sign of apoptosis.ConclusionsBased on the outcomes, it tends to be inferred that consequences of the present examination uncovered HLD in combination of 2:3 applies most encouraging systemic damage by reactive oxygen species generation and hyperlipidemia and necroapoptosis of the liver and heart. Hence, outcome of this study may help to formulate health care strategy and warns about the food habit in universal population regarding the use of hydrogenated and saturated fats (vanaspati ghee) in diet.


2021 ◽  
Author(s):  
Małgorzata Olszowy-Tomczyk

AbstractOxidative stress, associated with an imbalance between the oxidants (reactive oxygen species) and the antioxidants in the body, contributes to the development of many diseases. The body’s fight against reactive oxygen species is supported by antioxidants. Nowadays, there are too many analytical methods, but there is no one universal technique for assessing antioxidant properties. Moreover, the applied different ways of expressing the results lead to their incompatibility and unreasonable interpretation. The paper is a literature review concerning the most frequent ways of antioxidant activities expression and for an easy and universal method of the obtained results discussion. This paper is an attempt to point out their disadvantages and advantages. The manuscript can support the searching interpretation of the obtained results which will be a good tool for the development of a number of fields, especially medicine what can help in the future detection and treatment of many serious diseases. Graphic abstract


2010 ◽  
Vol 63 (11-12) ◽  
pp. 827-832 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic ◽  
Rada Jesic-Vukicevic

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.


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