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Antioxidants
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Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure
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Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 31993

Special Issue Editor

Dr. Luc Demaison

E-Mail Website
Guest Editor
Universite d' Auvergne Clermont-FD 1, INRA, Clermont-Ferrand, France

Special Issue Information

Dear Colleagues,

Cardiac failure can be a consequence of obesity and type-2 diabetes, perhaps through the development of oxidative stress. However, recent research indicated that abdominal obesity in rodents reduces cardiac oxidative stress, although the last is increased during type 2 diabetes. Vascular, cell-related oxidative stress is suspected to trigger abnormalities of coronary micro-vessels, leading to disrupted myocardial perfusion and, finally, cardiomyocyte contractile dysfunction. Myocardial inflammation seems also to be involved in parallel with mitochondrial oxidative stress. Pharmaceutical and/or dietary antioxidants may be very useful for preventing these deleterious alterations.

We invite you to submit your latest research findings or a review article to this Special Issue, which will bring together current research concerning cardiac consequences of obesity and/or diabetes, oxidative stress of endothelial cells, and/or cardiomyocytes and occurrence of diabetic cardiomyopathy. The role of various antioxidants on cardio-protection during type-2 diabetes will be appreciated. This research can include both in vitro and in vivo studies relating to any of the following topics: basic research about the transition between obesity and diabetic cardiomyopathy; and the influence of antioxidants on cardiac oxidative stress, inflammation, lipotoxicity, organelle (mitochondria, reticulum, and others) function, metabolism, cell death, fibrosis, contractile activity, and cardiac lethality in the different states related to diabetes (obesity, insulin resistance, and type-2 diabetes).

Dr. Luc Demaison
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (8 papers)

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Editorial

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3 pages, 173 KiB  
Editorial
Oxidative Stress and Obesity- and Type 2 Diabetes-Induced Heart Failure
by Luc Demaison
Antioxidants 2020, 9(8), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9080653 - 23 Jul 2020
Cited by 5 | Viewed by 1683
Abstract
Obesity is a risk factor for the development of type 2 diabetes (T2D), which is associated with cardiovascular diseases [...] Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)

Research

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17 pages, 1230 KiB  
Article
NADPH Oxidase 2 Mediates Myocardial Oxygen Wasting in Obesity
by Anne D. Hafstad, Synne S. Hansen, Jim Lund, Celio X. C. Santos, Neoma T. Boardman, Ajay M. Shah and Ellen Aasum
Antioxidants 2020, 9(2), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9020171 - 19 Feb 2020
Cited by 12 | Viewed by 2871
Abstract
Obesity and diabetes are independent risk factors for cardiovascular diseases, and they are associated with the development of a specific cardiomyopathy with elevated myocardial oxygen consumption (MVO2) and impaired cardiac efficiency. Although the pathophysiology of this cardiomyopathy is multifactorial and complex, [...] Read more.
Obesity and diabetes are independent risk factors for cardiovascular diseases, and they are associated with the development of a specific cardiomyopathy with elevated myocardial oxygen consumption (MVO2) and impaired cardiac efficiency. Although the pathophysiology of this cardiomyopathy is multifactorial and complex, reactive oxygen species (ROS) may play an important role. One of the major ROS-generating enzymes in the cardiomyocytes is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), and many potential systemic activators of NOX2 are elevated in obesity and diabetes. We hypothesized that NOX2 activity would influence cardiac energetics and/or the progression of ventricular dysfunction following obesity. Myocardial ROS content and mechanoenergetics were measured in the hearts from diet-induced-obese wild type (DIOWT) and global NOK2 knock-out mice (DIOKO) and in diet-induced obese C57BL/6J mice given normal water (DIO) or water supplemented with the NOX2-inhibitor apocynin (DIOAPO). Mitochondrial function and ROS production were also assessed in DIO and DIOAPO mice. This study demonstrated that ablation and pharmacological inhibition of NOX2 both improved mechanical efficiency and reduced MVO2 for non-mechanical cardiac work. Mitochondrial ROS production was also reduced following NOX2 inhibition, while cardiac mitochondrial function was not markedly altered by apocynin-treatment. Therefore, these results indicate a link between obesity-induced myocardial oxygen wasting, NOX2 activation, and mitochondrial ROS. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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16 pages, 4895 KiB  
Article
Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy
by Sumit Kar, Hamid R. Shahshahan, Bryan T. Hackfort, Santosh K. Yadav, Roopali Yadav, Tyler N. Kambis, David J. Lefer and Paras K. Mishra
Antioxidants 2019, 8(12), 638; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8120638 - 11 Dec 2019
Cited by 56 | Viewed by 6314
Abstract
Obesity increases the risk of developing diabetes and subsequently, diabetic cardiomyopathy (DMCM). Reduced cardioprotective antioxidant hydrogen sulfide (H2S) and increased inflammatory cell death via pyroptosis contribute to adverse cardiac remodeling and DMCM. Although exercise training (EX) has cardioprotective effects, it is [...] Read more.
Obesity increases the risk of developing diabetes and subsequently, diabetic cardiomyopathy (DMCM). Reduced cardioprotective antioxidant hydrogen sulfide (H2S) and increased inflammatory cell death via pyroptosis contribute to adverse cardiac remodeling and DMCM. Although exercise training (EX) has cardioprotective effects, it is unclear whether EX mitigates obesity-induced DMCM by increasing H₂S biosynthesis and mitigating pyroptosis in the heart. C57BL6 mice were fed a high-fat diet (HFD) while undergoing treadmill EX for 20 weeks. HFD mice developed obesity, hyperglycemia, and insulin resistance, which were reduced by EX. Left ventricle pressure-volume measurement revealed that obese mice developed reduced diastolic function with preserved ejection fraction, which was improved by EX. Cardiac dysfunction was accompanied by increased cardiac pyroptosis signaling, structural remodeling, and metabolic remodeling, indicated by accumulation of lipid droplets in the heart. Notably, EX increased cardiac H₂S concentration and expression of H₂S biosynthesis enzymes. HFD-induced obesity led to features of type 2 diabetes (T2DM), and subsequently DMCM. EX during the HFD regimen prevented the development of DMCM, possibly by promoting H₂S-mediated cardioprotection and alleviating pyroptosis. This is the first report of EX modulating H₂S and pyroptotic signaling in the heart. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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19 pages, 2031 KiB  
Article
Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats
by Steliana Ghibu, Cristina Elena Craciun, Razvan Rusu, Claudiu Morgovan, Cristina Mogosan, Luc Rochette, Adrian Florin Gal and Maria Dronca
Antioxidants 2019, 8(12), 636; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8120636 - 11 Dec 2019
Cited by 18 | Viewed by 4406
Abstract
Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today’s alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma [...] Read more.
Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today’s alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma oxidative stress induced by fructose intake, in rats. Sprague-Dawley rats (48 animals) were randomized into two series (n = 24): rats fed with standard chow or with standard chow supplemented with 60% fructose. In each of the two series, for 2 weeks/month over 12 weeks, a group of rats (n = 12) was intraperitoneally injected with NaCl 0.9%, and a second group (n = 12) received AL 50 mg/kg/day. Body weight, glycemia, and systolic blood pressure were monitored throughout the study. After 12 weeks, IR, plasma lipoproteins, uric acid, transaminase activities, and oxidative stress markers were assessed. The high fructose-enriched diet induced cardiometabolic disorders (hypertension, hyperglycemia, IR and dyslipidemia), an increase in uric acid concentration, transaminase activities and C-reactive protein level. This diet also enhanced plasma products of lipid and protein oxidation, homocysteine level, and decreased GSH/GSSG ratio. In this field, there is evidence to indicate that oxidative stress plays an important role in the etiology of diabetic complications. AL discontinuous treatment prevents the metabolic disorders induced by fructose intake, reduced plasma lipid and protein oxidation-products, and restored the GHS/GSSG ratio. Our study proves a promising potential of the chronic-discontinuous treatment of AL and highlights the pleiotropic effects of this antioxidant substance in metabolic disorders such as diabetes. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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10 pages, 442 KiB  
Article
Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease
by Mia Steyn, Karima Zitouni, Frank J Kelly, Paul Cook and Kenneth A Earle
Antioxidants 2019, 8(12), 629; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8120629 - 07 Dec 2019
Cited by 7 | Viewed by 3375
Abstract
Women with type 2 diabetes (T2DM) have an increased susceptibility of developing cardio-renal disease compared to men, the reasons and the mechanisms of this vulnerability are unclear. Since oxidative stress plays a key role in the development of cardio-renal disease, we investigated the [...] Read more.
Women with type 2 diabetes (T2DM) have an increased susceptibility of developing cardio-renal disease compared to men, the reasons and the mechanisms of this vulnerability are unclear. Since oxidative stress plays a key role in the development of cardio-renal disease, we investigated the relationship between sex, plasma antioxidants status (glutathione peroxidase (GPx-3 activity), vitamin E and selenium), and adiposity in patients with T2DM at high risk of cardio-renal disease. Women compared to men had higher GPx-3 activity (p = 0.02), bio-impedance (p ≤ 0.0001), and an increase in waist circumference in relation to recommended cut off-points (p = 0.0001). Waist circumference and BMI were negatively correlated with GPx-3 activity (p ≤ 0.05 and p ≤ 0.01, respectively) and selenium concentration (p ≤ 0.01 and p ≤ 0.02, respectively). In multiple regression analysis, waist circumference and sex were independent predictors of GPx-3 activity (p ≤ 0.05 and p ≤ 0.05, respectively). The data suggest that increased central fat deposits are associated with reduced plasma antioxidants which could contribute to the future risk of cardio-renal disease. The increased GPx-3 activity in women could represent a preserved response to the disproportionate increase in visceral fat. Future studies should be aimed at evaluating if the modulation of GPx-3 activity reduces cardio-renal risk in men and women with T2DM. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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22 pages, 4821 KiB  
Article
Effect of Rosmarinic Acid and Sinapic Acid on Oxidative Stress Parameters in the Cardiac Tissue and Serum of Type 2 Diabetic Female Rats
by Maria Zych, Weronika Wojnar, Sławomir Borymski, Katarzyna Szałabska, Piotr Bramora and Ilona Kaczmarczyk-Sedlak
Antioxidants 2019, 8(12), 579; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8120579 - 22 Nov 2019
Cited by 35 | Viewed by 4691
Abstract
Cardiovascular diseases are one of the most common complications of type 2 diabetes. They are considered the leading cause of death among diabetics. One of the mechanisms underlying diabetic cardiovascular complications is oxidative stress. Many phenolic acids are regarded as antioxidants. The aim [...] Read more.
Cardiovascular diseases are one of the most common complications of type 2 diabetes. They are considered the leading cause of death among diabetics. One of the mechanisms underlying diabetic cardiovascular complications is oxidative stress. Many phenolic acids are regarded as antioxidants. The aim of the study was to investigate the effect of rosmarinic acid (RA) and sinapic acid (SA) on oxidative stress parameters in the cardiac tissue and serum of type 2 diabetic female rats. Additionally, the effect of these compounds on glucose homeostasis and lipid profile in the serum was evaluated. Type 2 diabetes was induced with high-fat diet and streptozotocin. RA at the doses of 10 and 50 mg/kg and SA at the doses of 5 and 25 mg/kg were administrated orally for 28 days. Untreated diabetic rats exhibited unfavorable changes in glucose metabolism and lipid profile. Changes in the enzymatic and non-enzymatic markers indicated the onset of oxidative stress in these animals. The results showed that the higher doses of the tested phenolic acids—50 mg/kg of RA and 25 mg/kg of SA—revealed beneficial effects on oxidative stress in the cardiac tissue of diabetic rats. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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25 pages, 3246 KiB  
Article
Dietary EPA Increases Rat Mortality in Diabetes Mellitus, a Phenomenon Which Is Compensated by Green Tea Extract
by Thibault Leger, Beibei He, Kasra Azarnoush, Chrystèle Jouve, Jean-Paul Rigaudiere, Florent Joffre, Damien Bouvier, Vincent Sapin, Bruno Pereira and Luc Demaison
Antioxidants 2019, 8(11), 526; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8110526 - 04 Nov 2019
Cited by 5 | Viewed by 3819
Abstract
Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to [...] Read more.
Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to determine the effects of EPA, green tea extract (GTE), and a combination of both on the cardiac consequences of diabetes mellitus, induced in Wistar rats by injection of a low dose of streptozotocin (33 mg/kg) combined with a high fat diet. Cardiac mechanical function, coronary reactivity, and parameters of oxidative stress, inflammation, and energy metabolism were evaluated. In the context of diabetes, GTE alone limited several diabetes-related symptoms such as inflammation. It also slightly improved coronary reactivity and considerably enhanced lipid metabolism. EPA alone caused the rapid death of the animals, but this effect was negated by the addition of GTE in the diet. EPA and GTE combined enhanced coronary reactivity considerably more than GTE alone. In a context of significant oxidative stress such as during diabetes mellitus, EPA enrichment constitutes a risk factor for animal survival. It is essential to associate it with the antioxidants contained in GTE in order to decrease mortality rate and preserve cardiac function. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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Review

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11 pages, 1218 KiB  
Review
Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients
by Daniela Pellegrino, Daniele La Russa and Alessandro Marrone
Antioxidants 2019, 8(12), 594; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox8120594 - 28 Nov 2019
Cited by 22 | Viewed by 4360
Abstract
Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity [...] Read more.
Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors. Full article
(This article belongs to the Special Issue Oxidative Stress and Obesity- and Type-2 Diabetes-Induced Heart Failure)
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