scholarly journals Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures

2020 ◽  
Vol 21 (19) ◽  
pp. 7060
Author(s):  
Giovanni Pagano ◽  
Federico V. Pallardó ◽  
Alex Lyakhovich ◽  
Luca Tiano ◽  
Maria Rosa Fittipaldi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Clinical Studies ◽  
Antioxidant Properties ◽  
Cardiovascular Disorders ◽  
Combined Administration

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential–and distinct—roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.

scholarly journals Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

2019 ◽  
Vol 8 (9) ◽  
pp. 1385 ◽  
Author(s):  
Burgos-Morón ◽  
Abad-Jiménez ◽  
Marañón ◽  
Iannantuoni ◽  
Escribano-López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Β Cells ◽  
The Relationship ◽  
And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

scholarly journals Platelet Mitochondrial Dysfunction is Evident in Type 2 Diabetes in Association with Modifications of Mitochondrial Anti-Oxidant Stress Proteins

2011 ◽  
Vol 120 (04) ◽  
pp. 248-251 ◽  
Author(s):  
C. Avila ◽  
R. Huang ◽  
M. Stevens ◽  
A. Aponte ◽  
D. Tripodi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Oxidant Stress ◽  
Mitochondrial Protein ◽  
Protein Carbonylation ◽  
Mitochondrial Enzymes ◽  
Anti Oxidant ◽  
Type 2 Diabetic

AbstractMitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells.A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls.As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This ‘stress-signature’ in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as “accessible human tissue”, may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.

Taurine ameliorates mitochondrial dysfunction and oxidative stress in the heart of rats with type 2 diabetes

2016 ◽  
Vol 42 (4) ◽  
pp. 294 ◽  
Author(s):  
Nataliia Gorbenko ◽  
Oleksiy Borikov ◽  
Olga Ivanova ◽  
Tatiana Zvyagina ◽  
Katerina Taran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
And Oxidative Stress

scholarly journals Oxidative stress and increasing antioxidant defence in type 2 diabetes

2020 ◽  
Vol 1 (3) ◽  
pp. 127-136
Author(s):  
Khaider Khamzyarovich Sharafetdinov ◽  
Oxana A. Plotnikova ◽  
Victory V. Pilipenko ◽  
Dmitry B. Nikitjuk
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Antioxidant Properties ◽  
Vascular Complications ◽  
Food Products ◽  
Antioxidant Vitamins ◽  
Biologically Active ◽  
Number Of Patients

The article discusses topical issues reflecting the high prevalence of diabetes mellitus (DM), the continuing trend towards an increase in the number of patients, the high incidence of vascular complications that lead to early disability and high mortality. The review presents current data on the role of oxidative stress in the development and progression of vascular complications in patients with type 2 diabetes, as well as the mechanisms underlying the imbalance between prooxidants and the antioxidant defense system in this disease. The article presents the role of a balanced diet in achieving metabolic goals and increasing antioxidant protection in type 2 diabetes. The review provides data on the role of vitamins in the correction of metabolic disorders in type 2 diabetes. The increased need for antioxidant vitamins in diabetes is due to impaired glucose metabolism in this category of patients. Food products, which contain polyphenolic compounds, have a pronounced antioxidant and antithrombotic activity, which favorably affect metabolic parameters that contribute to weight loss. Thus, one of the ways to optimize the therapeutic nutrition of patients with type 2 diabetes is the inclusion in the standard hypocaloric diet of specialized food products containing antioxidant vitamins and minor biologically active substances with pronounced antioxidant properties.

scholarly journals Mitoprotective Clinical Strategies in Type 2 Diabetes and Fanconi Anemia Patients: Suggestions for Clinical Management of Mitochondrial Dysfunction

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 82 ◽  
Author(s):  
Giovanni Pagano ◽  
Federico V. Pallardó ◽  
Beatriz Porto ◽  
Maria Rosa Fittipaldi ◽  
Alex Lyakhovich ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Fanconi Anemia ◽  
Genetic Disease ◽  
Clinical Studies ◽  
Clinical Progression ◽  
Clinical Strategies

Oxidative stress (OS) and mitochondrial dysfunction (MDF) occur in a number of disorders, and several clinical studies have attempted to counteract OS and MDF by providing adjuvant treatments against disease progression. The present review is aimed at focusing on two apparently distant diseases, namely type 2 diabetes (T2D) and a rare genetic disease, Fanconi anemia (FA). The pathogenetic links between T2D and FA include the high T2D prevalence among FA patients and the recognized evidence for OS and MDF in both disorders. This latter phenotypic/pathogenetic feature—namely MDF—may be regarded as a mechanistic ground both accounting for the clinical outcomes in both diseases, and as a premise to clinical studies aimed at counteracting MDF. In the case for T2D, the working hypothesis is raised of evaluating any in vivo decrease of mitochondrial cofactors, or mitochondrial nutrients (MNs) such as α-lipoic acid, coenzyme Q10, and l-carnitine, with possibly combined MN-based treatments. As for FA, the established knowledge of MDF, as yet only obtained from in vitro or molecular studies, prompts the requirement to ascertain in vivo MDF, and to design clinical studies aimed at utilizing MNs toward mitigating or delaying FA’s clinical progression. Altogether, this paper may contribute to building hypotheses for clinical studies in a number of OS/MDF-related diseases.

scholarly journals Melatonin protects against uric acid-induced mitochondrial dysfunction, oxidative stress, and triglyceride accumulation in C2C12myotubes

2017 ◽  
Vol 122 (4) ◽  
pp. 1003-1010 ◽  
Author(s):  
Gerald J. Maarman ◽  
Brittany M. Andrew ◽  
Dee M. Blackhurst ◽  
Edward O. Ojuka
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Uric Acid ◽  
Adverse Effects ◽  
Mitochondrial Dysfunction ◽  
Independent Predictor ◽  
Triglyceride Accumulation ◽  
Triglyceride Content

Excess uric acid has been shown to induce oxidative stress, triglyceride accumulation, and mitochondrial dysfunction in the liver and is an independent predictor of type-2 diabetes. Skeletal muscle plays a dominant role in type 2 diabetes and presents a large surface area to plasma uric acid. However, the effects of uric acid on skeletal muscle are underinvestigated. Our aim was therefore to characterize the effects of excessive uric acid on oxidative stress, triglyceride content, and mitochondrial function in skeletal muscle C2C12myotubes and assess how these are modulated by the antioxidant molecule melatonin. Differentiated C2C12myotubes were exposed to 750 µM uric acid or uric acid + 10 nM melatonin for 72 h. Compared with control, uric acid increased triglyceride content by ~237%, oxidative stress by 32%, and antioxidant capacity by 135%. Uric acid also reduced endogenous ROUTINE respiration, complex II-linked oxidative phosphorylation, and electron transfer system capacities. Melatonin counteracted the effects of uric acid without further altering antioxidant capacity. Our data demonstrate that excess uric acid has adverse effects on skeletal muscle similar to those previously reported in hepatocytes and suggest that melatonin at a low physiological concentration of 10 nM may be a possible therapy against some adverse effects of excess uric acid.NEW & NOTEWORTHY Few studies have investigated the effects of uric acid on skeletal muscle. This study shows that hyperuricemia induces mitochondrial dysfunction and triglyceride accumulation in skeletal muscle. The findings may explain why hyperuricemia is an independent predictor of diabetes.

Oxidative Stress and Mitochondrial Dysfunction in Type 2 Diabetes

2011 ◽  
Vol 17 (36) ◽  
pp. 3947-3958 ◽  
Author(s):  
Victor M. Victor ◽  
Milagros Rocha ◽  
Raul Herance ◽  
Antonio Hernandez-Mijares
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction

scholarly journals Hypoglycaemic and Antioxidant Properties of Acrocomia aculeata (Jacq.) Lodd Ex Mart. Extract Are Associated with Better Vascular Function of Type 2 Diabetic Rats

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2856
Author(s):  
Tamaeh Monteiro-Alfredo ◽  
Sara Oliveira ◽  
Andreia Amaro ◽  
Daniela Rosendo-Silva ◽  
Katia Antunes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Vascular Function ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Antioxidant Defences ◽  
Acrocomia Aculeata ◽  
Type 2 Diabetic

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). Acrocomia aculeata (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2. Control Wistar (W-Ctrl) and non-obese type 2 diabetic Goto–Kakizaki (GK-Ctrl) rats were treated for 30 days with 200 mg.kg−1 aqueous extract of Aa (EA-Aa) (Wistar, W-EA-Aa/GK, GK-EA-Aa). EA-Aa was able to reduce fasting glycaemia and triglycerides of GK-EA-Aa by improving proteins related to glucose and lipid metabolism, such as GLUT-4, PPARγ, AMPK, and IR, when compared to GK-Ctrl. It also improved viability of 3T3-L1 pre-adipocytes exposed by H2O2. EA-Aa also increased the levels of catalase in the aorta and kidney, reduced oxidative stress and increased relaxation of the aorta in GK-treated rats in relation to GK-Ctrl, in addition to the protective effect against oxidative stress in HMVec-D cells. We proved the direct antioxidant potential of the chemical compounds of EA-Aa, the increase in antioxidant defences in a tissue-specific manner and hypoglycaemic properties, improving vascular function in type 2 diabetes. EA-Aa and its constituents may have a therapeutic potential for the treatment of DM2 complications.

Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice

2009 ◽  
Vol 297 (3) ◽  
pp. H1069-H1077 ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Shouji Matsushima ◽  
Naoki Inoue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Exercise Capacity ◽  
Mitochondrial Function ◽  
Exercise Intolerance ◽  
Whole Body

Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (V̇o2). The work (vertical distance × body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak V̇o2. Mitochondrial ADP-stimulated respiration, electron transport chain complex I and III activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes.

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