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Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: A double-blind, randomized controlled study

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... Endothelial dysfunction, a main mechanism underlying the development of arteriosclerotic disease, is considered a significant predictor of cardiovascular risk [44,45]. The effect of CoQ10 supplementation on the modulation of endothelial function has been evaluated in patients with type 2 diabetes mellitus, CAD, or in elderly people [46][47][48]. These results showed that flow-mediated dilation, or nitroglycerin-mediated dilation and the extracellular superoxide dismutase activity increased in most of the subjects treated with CoQ10, attributing this effect to its antioxidant and anti-inflammatory activity [35,48,49]. ...
... The effect of CoQ10 supplementation on the modulation of endothelial function has been evaluated in patients with type 2 diabetes mellitus, CAD, or in elderly people [46][47][48]. These results showed that flow-mediated dilation, or nitroglycerin-mediated dilation and the extracellular superoxide dismutase activity increased in most of the subjects treated with CoQ10, attributing this effect to its antioxidant and anti-inflammatory activity [35,48,49]. Although the mechanisms of CoQ10 in modulating endothelial function are still unclear, it has been suggested that it could be partly attributed to its capacity for reducing oxidative stress and inflammation, particularly in myocardial and endothelial cells [50] and decreasing the rate of activation of NO to peroxynitrite by superoxide radicals, which could improve both vascular tone and endothelial function [51]. ...
... In fact, in patients with HF, treatment with CoQ10 (400 mg/d for three months) resulted in significant improvements in peripheral endothelial function, determined by the reactive hyperemia index, accompanied by low levels of oxidized-LDL [52]. CoQ10 has also been shown to improve endothelial function in patients with CAD [48] and type 2 diabetes mellitus [53]. ...
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Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD.
... Singh et al. (1998) also documented that 120 mg/day of CoQ10 supplementation provided rapid protective effects in patients with myocardial infarction if administered within 3 days of the onset of symptoms. In another study by Tiano et al. (2007), thirty-eight patients with CAD were randomized into two groups to consume either 100 mg of CoQ10 three times daily (300 mg/day) or placebo for 1 month. A total of 33 patients completed the study and results demonstrated a significant rise in extracellular superoxide dismutase (ecSOD) activity and endothelium-dependent relaxation (Tiano et al. 2007). ...
... In another study by Tiano et al. (2007), thirty-eight patients with CAD were randomized into two groups to consume either 100 mg of CoQ10 three times daily (300 mg/day) or placebo for 1 month. A total of 33 patients completed the study and results demonstrated a significant rise in extracellular superoxide dismutase (ecSOD) activity and endothelium-dependent relaxation (Tiano et al. 2007). In addition, CoQ10 supplementation (60 mg twice a day) for 28 days to patients with acute coronary disease was associated with a significant reduction in thiobarbituric acid reactive substances, MDA and diene conjugates, indicating an overall decrease in oxidative stress (Singh and Niaz 1999). ...
... There are trials in patients with CAD evaluating the effects of CoQ10 on biomarkers of inflammation and oxidative stress with controversial results. Tiano et al. (2007) administered CoQ10 (300 mg/day) to people with CAD for 1 month, and they found that those patients' ecSOD and endothelium-dependent vasodilatation were improved after supplementation. Antioxidant enzymes including SOD, CAT, and GPx are the first line of defense against reactive oxygen species (Bocci and Valacchi 2013), and a reduction in their activities contributes to the enhanced oxidative stress in people with CAD (Lee et al. 2012c). ...
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Objective Systemic inflammation and oxidative stress significantly contribute in developing coronary artery disease (CAD). This systematic review and meta-analysis was aimed to determine the effects of coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress among patients with CAD. Methods The electronic databases including MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library databases were systematically searched until Oct 2018. The quality assessment and heterogeneity of the selected randomized clinical Trials (RCTs) were examined using the Cochrane Collaboration risk of bias tool, and Q and I² tests, respectively. Given the presence of heterogeneity, random-effects model or fixed-effect model were used to pool standardized mean differences (SMDs) as summary effect sizes. Results A total of 13 clinical RCTs of 912 potential citations were found to be eligible for the current meta-analysis. The pooled findings for biomarkers of inflammation and oxidative stress demonstrated that CoQ10 supplementation significantly increased superoxide dismutase (SOD) (SMD 2.63; 95% CI, 1.17, 4.09, P < 0.001; I² = 94.5%) and catalase (CAT) levels (SMD 1.00; 95% CI, 0.57, 1.43, P < 0.001; I² = 24.5%), and significantly reduced malondialdehyde (MDA) (SMD − 4.29; 95% CI − 6.72, − 1.86, P = 0.001; I² = 97.6%) and diene levels (SMD − 2.40; 95% CI − 3.11, − 1.68, P < 0.001; I² = 72.6%). We did not observe any significant effect of CoQ10 supplementation on C-reactive protein (CRP) (SMD − 0.62; 95% CI − 1.31, 0.08, P = 0.08; I² = 87.9%), tumor necrosis factor alpha (TNF-α) (SMD 0.22; 95% CI − 1.07, 1.51, P = 0.73; I² = 89.7%), interleukin-6 (IL-6) (SMD − 1.63; 95% CI − 3.43, 0.17, P = 0.07; I² = 95.2%), and glutathione peroxidase (GPx) levels (SMD 0.14; 95% CI − 0.77, 1.04, P = 0.76; I² = 78.7%). Conclusions Overall, this meta-analysis demonstrated CoQ10 supplementation increased SOD and CAT, and decreased MDA and diene levels, but did not affect CRP, TNF-α, IL-6, and GPx levels among patients with CAD.
... Як антиоксидант, КоQ10 перевершує всі інші природні антиоксиданти й тому вважається найбільш перспективним для застосування в клінічній практиці. Втрата убіхінону прогресивно зростає при фізичних і емоційних навантаженнях, при частих простудних захворюваннях, хронічному стресі, що обумовлює ймовірність розвитку його дефіциту [26,28,40]. Особливого значення набуває дефіцит убіхінону при низці захворювань. ...
... Особливого значення набуває дефіцит убіхінону при низці захворювань. Клінічними дослідженнями встановлено, що розвиток багатьох обмінних і дистрофічних захворювань, патологія імунної системи, передчасне старіння, надмірна маса тіла тісно пов'язані з недоліком енергоутворення в організмі і пошкодженням клітинних генераторів енергії [40]. ...
... КоQ10безпечний і ефективний додатковий засіб для лікування широкого спектра серцево-судинних захворювань, використання якого не тільки поліпшує клінічні результати, а й дозволяє знизити сумарні витрати на лікування [2,3,26,27]. У дослідженнях установлено поліпшення функціональної потужності, ендотеліальної функції та скоротливості лівого шлуночка без будь-яких побічних ефектів [37,40,41,46]. ...
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В статье изложены результаты анализа литературы, посвященные обсуждению преимуществ и потенциальных возможностей альфа-липоевой кислоты и коэнзима Q10 (убихинон) у пациентов с кардиоваскулярными заболеваниями, хроническими диффузными заболеваниями печени, сахарным диабетом и другими метаболическими состояниями. Сегодня ведется активный поиск дополнительных источников, способствующих улучшению углеводного и липидного обмена, метаболических и энергетических процессов в организме, которые повышают устойчивость сердечно-сосудистой системы и печени к различным нарушениям и патологическим воздействиям, а также способствуют восстановлению функций различных органов при их повреждениях. В Украине комбинация альфа-липоевой кислоты и коэнзима Q10 представлена отечественным комплексом Липофарм от компании «Фармаком».
... These functions provide a strong rationale for its clinical use to treat cardiovascular disease (CVD). CoQ10 has improved endothelium-dependent vasodilation, as measured by FMD, in patients with type 2 diabetes [23,24], or coronary artery disease (CAD) [25]. However, the evidence of its effect on ED in subjects without clinical manifestations of atherosclerosis-related disease is limited. ...
... However, the evidence of its effect on ED in subjects without clinical manifestations of atherosclerosis-related disease is limited. It has been reported that ubiquinone, the oxidized form of CoQ10, was not able to improve EF in healthy subjects with cardiovascular risk factors, in contrast to what has been observed in the secondary prevention setting [25,26]. Given the significantly higher bioavailability of orally administered ubiquinol compared with ubiquinone [27] and its direct antioxidant activity, this study assesses whether 8-week ubiquinol supplementation enhances endothelium-dependent vasodilation in adults with moderate untreated dyslipidemia and without evidence of CVD. ...
... A further exploratory analysis was performed without the data from the 20 subjects whose total CoQ10 levels at the end of the study exceeded 500 µmol/mol cholesterol, corresponding to a concentration of 2.5 µg/mL in subjects with a total cholesterol level of 220 mg/dL. The value of 500 µmol/mol was taken from previous studies, including one from our group, where it was identified as the dosage threshold conferring cardiovascular benefit on CVD patients [25]. It was thus reasonable to hypothesize that a saturating effect above this level should weaken the correlation. ...
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In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130-200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%-6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%; p < 0.001) and a marked increase in plasma CoQ10, either total (p < 0.001) and reduced (p < 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (p = 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (p = 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.
... whereas there was no change in the control group. 12 Hamilton et al found brachial artery FMD to be improved by 1% after CoQ10 supplementation for 12 weeks in patients with type 2 diabetes. 32 A meta-analysis combined five eligible randomised controlled trials showed that treatment with CoQ10 significantly improved in endothelial function assessed peripherally by FMD (standard mean difference 1.70, 95% CI 1.00 to 2.4, p<0.0001). ...
... 11 The detailed mechanism might involve altering local vascular oxidative stress. 12 32 Tiano et al's study indicated that improvements of extracellular superoxide dismutase (ecSOD) activity might be related to CoQ10 capability of enhancing endothelial function. 12 In this study, patients with lower levels of ecSOD had greater improvement in endothelial function. ...
... 12 32 Tiano et al's study indicated that improvements of extracellular superoxide dismutase (ecSOD) activity might be related to CoQ10 capability of enhancing endothelial function. 12 In this study, patients with lower levels of ecSOD had greater improvement in endothelial function. ...
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Introduction Endothelial and cardiac dysfunction are highly prevalent and are associated with cardiovascular morbidity and mortality among patients undergoing dialysis. For patients undergoing dialysis, no study has explored the effect of supplementation of coenzyme Q10 (CoQ10) on endothelial function. To our best of knowledge, only two small sample studies focused on the efficacy of supplementation of CoQ10 on cardiac function. However, the effect of CoQ10 supplementation on cardiac function remains uncertain in patients who undergo haemodialysis. The aim of this study is to explore whether CoQ10 supplementation can improve endothelial and cardiac function in patients undergoing haemodialysis. Methods and analysis This is a pilot randomised controlled study. Eligible patients undergoing haemodialysis in our haemodialysis centre will be randomly allocated to the CoQ10 and control groups. The follow-up time is 12 months. The primary outcome is to assess the change of brachial artery endothelial-dependent flow-mediated dilation, left ventricular systolic function, diastolic function and Myocardial Performance Index at 12 months from baseline. Secondary outcomes are death or hospitalisation due to cardiovascular events, all-cause mortality, change of CoQ10 concentration, the ratio of ubiquinol to ubiquinone, the change of oxidative stress markers (including malondialdehyde and 8-hydroxy-deoxyguanosine) and Left Ventricular Mass Index. Ethics and dissemination Risks associated with CoQ10 are minor, even at doses as high as 1800 mg according to previous studies. The trial has received ethics approval from the Medical Ethics Committee for Clinical Trials of Drugs, the 306th Hospital of Chinese PLA. The results of the study are expected to be published in a peer-reviewed journal and presented at academic conferences. Trial registration number ChiCTR1900022258.
... Moreover, these positive effects appear to be mediated by improved mitochondrial function and the reduction in mtROS-mediated EC dysfunction and reduced EC senescence [535][536][537][538]. There are also reports of improvement in endothelial function in T2D and CVD following CoQ supplementation in patients optimally treated with statins [539,540]. These data would appear to strengthen further the argument for combining these two preparations in an attempt to mitigate CVD risk in patients with neuroprogressive illnesses [539,540]. ...
... There are also reports of improvement in endothelial function in T2D and CVD following CoQ supplementation in patients optimally treated with statins [539,540]. These data would appear to strengthen further the argument for combining these two preparations in an attempt to mitigate CVD risk in patients with neuroprogressive illnesses [539,540]. Given the above information, it probably comes as no surprise to learn that there are several studies suggesting that CoQ arrests the development of atherosclerosis (reviewed in [541]), CVD morbidity and CVD mortality [542], although it should be noted that the results reported by such studies are somewhat inconsistent [543]. ...
Article
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Background: Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. Main text: Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. Conclusions: Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
... Acting as an antioxidant, CoQ10 is also capable of preventing NO oxidation to peroxynitrite and prolonging a vasodilatation effect. These findings are supported by the results obtained by Belardinelli et al., 2006, in patients with chronic heart failure [45] and Tiano et al., 2007, in patients with ischemic heart disease using oral CoQ 10 form [46]. Kozaeva et al., 2017, has also demonstrated vasodilation of isolated aortic rings of healthy rats after incubation but with the studied form of ubiquinol [47]. In addition, previously we spotted an increase in the endothelium-dependent expansion of isolated segments of pulmonary artery against the background of intravenous administration of ubiquinol in the experiment on the MCT-induced PH model in male rats [33]. ...
... Acting as an antioxidant, CoQ10 is also capable of preventing NO oxidation to peroxynitrite and prolonging a vasodilatation effect. These findings are supported by the results obtained by Belardinelli et al., 2006, in patients with chronic heart failure [45] and Tiano et al., 2007, in patients with ischemic heart disease using oral CoQ 10 form [46]. Kozaeva et al., 2017, has also demonstrated vasodilation of isolated aortic rings of healthy rats after incubation but with the studied form of ubiquinol [47]. In addition, previously we spotted an increase in the endothelium-dependent expansion of isolated segments of pulmonary artery against the background of intravenous administration of ubiquinol in the experiment on the MCT-induced PH model in male rats [33]. ...
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Ubiquinol exhibits anti-inflammatory and antioxidant properties. Selenium is a part of a number of antioxidant enzymes. The monocrotaline inducible model of pulmonary hypertension used in this study includes pathological links that may act as an application for the use of ubiquinol with high bioavailability and selenium metabolic products. On day 1, male and female rats were subcutaneously injected with a water-alcohol solution of monocrotaline or only water-alcohol solution. On days 7 and 14, some animals were intravenously injected with either ubiquinol’s vehicle or solubilized ubiquinol, or orally with selenium powder daily, starting from day 7, or received both ubiquinol + selenium. Magnetic resonance imaging of the lungs was performed on day 20. Hemodynamic parameters and morphometry were measured on day 22. An increased right ventricle systolic pressure in relation to control was demonstrated in all groups of animals of both sexes, except the group of males receiving the combination of ubiquinol + selenium. The relative mass of the right ventricle did not differ from the control in all groups of males and females receiving either ubiquinol alone or the combination. Magnetic resonance imaging revealed impaired perfusion in almost all animals examined, but pulmonary fibrosis developed in only half of the animals in the ubiquinol group. Intravenous administration of ubiquinol has a protective effect on monocrotaline-induced pulmonary hypertension development resulting in reduced right ventricle hypertrophy, and lung mass. Ubiquinol + selenium administration resulted in a less severe increase in the right ventricle systolic pressure in male rats but not in females 3 weeks after the start of the experiment. This sex-dependent effect was not observed in the influence of ubiquinol alone.
... CoQ 10 is useful in preventing several CV diseases, as ischemic heart disease, chronic heart failure, hypertension, CV surgery, arrhythmias, and statin-induced cardiomyopathy. The possible mechanisms of CoQ 10 in CVD include improvement of myocardial energy production, reduction of free radical production, increasing of myocardial CoQ 10 content, and improvement in endothelial function by counteracting nitric oxide oxidation [40]. ...
... CoQ 10 increased extracellular superoxide dismutase activity in the endothelium in ischemic heart disease. This finding indicates that supplementary therapy with CoQ 10 can improve endothelial dysfunction [40,45]. ...
Chapter
Coenzyme Q10 is a cofactor for mitochondrial respiratory chain complexes connected with adenosine triphosphate production in oxidative phosphorylation. It has a fundamental role in cellular bioenergetics and therefore is important for its application in mitochondrial non-communicable diseases (NCDs). Its reduced form, ubiquinol, acts as an antioxidant, scavenging free oxygen radicals. NCDs are closely related to metabolic syndrome. NCDs are noninfectious and nontranmissible, and their origin is a combination of genetic, physiological, and lifestyle factors. NCDs are responsible for 71% of all deaths in the world. The most common NCDs are cardiovascular diseases, cancers, respiratory tract disease, diabetes, and chronic kidney diseases. Annually, 17.9 million people become ill with cardiovascular diseases, 9 million people with cancers, 3.9 million people with respiratory tract diseases, and 1.6 million people with diabetes. The prevalence, development, and progression of chronic kidney diseases have reached epidemic proportions. In all NCDs, oxidative stress and mitochondrial dysfunction play crucial roles. Prevention of development of mitochondrial NCDs by coenzyme Q10 is one of the basic forms of protection of human health.
... 32 Supplementation with 100 mg of CoQ 10 three times a day in a controlled, randomized study resulted in a significant increase in ecSOD activity in those patients who were deficient in ecSOD. 33 As previously mentioned, a possible scenario could be that CoQ 10 salvages NO − by scavenging free radicals. In addition, NO − can interact with cellular targets, can participate in intracellular signaling, and can increase the expression of ecSOD. ...
... 29,34 A higher ecSOD activity could further protect NO − from becoming inactivated by O 2 − . 33 The mechanism in lowering blood pressure for hypertensive patients can also be attributed to this preservation of the endothelium. Rosenfeldt et al reviewed eight different trials, four placebo-controlled and four non-placebo-controlled trials, in which patients were given 100-200 mg of CoQ 10 for 8-12 weeks. ...
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Taylor C Rodick,1 Donna R Seibels,2 Jeganathan Ramesh Babu,1 Kevin W Huggins,1 Guang Ren,3 Suresh T Mathews2 1Department of Nutrition, Dietetics, & Hospitality Management, Auburn University, Auburn, 2Department of Nutrition and Dietetics, Samford University, 3Medicine-Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Coenzyme Q10 (CoQ10), an endogenously produced compound, is found in all human cells. Within the mitochondria, it plays a substantial role in energy production by acting as a mobile electron carrier in the electron transport chain. Outside the mitochondria, it acts as an excellent antioxidant by sequestering free radicals and working synergistically with other antioxidants, including vitamin E. Dietary contribution is limited, making endogenous production the primary source for optimal function. Now widely available as an over-the-counter supplement, CoQ10 has gained attention for its possible therapeutic use in minimizing the outcomes of certain metabolic diseases, notably cardiovascular disease, diabetes, neurodegenerative disease, and cancer. Research has shown positive results in subjects supplemented with CoQ10, especially in relation to upregulating antioxidant capability. Emerging research suggests beneficial effects of CoQ10 supplementation in individuals on statin medications. CoQ10 supplementation in individuals participating in strenuous exercise seems to exert some beneficial effects, although the data are conflicting with other types of physical activity. This broad review of current CoQ10 literature, while outlining its physiological/functional significance in health and disease conditions, also offers a dietitian’s perspective on its potential use as a supplement in the promotion of health and management of disease conditions. Keywords: coenzyme Q, antioxidant, oxidative stress, dietary supplement, statin
... Endothelial dysfunction is also described as being involved in the deterioration of cardiac function, especially in conditions of metabolic disease [40]. Several studies have demonstrated the effect of CoQ 10 supplementation on endothelial function in patients with type 2 diabetes mellitus, CAD or in elderly people [41][42][43], showing that flow-mediated dilation (FMD) or nitroglycerin-mediated dilation (NMD) and extracellular superoxide dismutase activity increased in most of the subjects treated with CoQ 10 , which could be attributed to its antioxidant and anti-inflammatory activity [36,43,44]. This effect of CoQ 10 results in reduced levels of oxidative stress markers such as advanced glycation end products [45] and a decreased rate of inactivation of NO to peroxynitrite by superoxide radicals that could improve vascular tone as well as endothelial function. ...
... Endothelial dysfunction is also described as being involved in the deterioration of cardiac function, especially in conditions of metabolic disease [40]. Several studies have demonstrated the effect of CoQ 10 supplementation on endothelial function in patients with type 2 diabetes mellitus, CAD or in elderly people [41][42][43], showing that flow-mediated dilation (FMD) or nitroglycerin-mediated dilation (NMD) and extracellular superoxide dismutase activity increased in most of the subjects treated with CoQ 10 , which could be attributed to its antioxidant and anti-inflammatory activity [36,43,44]. This effect of CoQ 10 results in reduced levels of oxidative stress markers such as advanced glycation end products [45] and a decreased rate of inactivation of NO to peroxynitrite by superoxide radicals that could improve vascular tone as well as endothelial function. ...
Article
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Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q 10 (CoQ 10) has been described as having multiple functions, such as oxidant action in the generation of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ 10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ 10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ 10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ 10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q 10 or Qter ® , to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ 10 possible in clinical practice.
... Questi sono rappresentati principalmente dalla superossido dismutasi extracellulare (ecSOD), un enzima in grado di neutralizzare il superossido [204]. Partendo dall'ipotesi che il CoQ10 possa influenzare positivamente la funzione endoteliale, misurata tramite FMD, molti studi sono stati condotti su soggetti affetti da patologie notoriamente collegate all'aterosclerosi, quali il diabete mellito di tipo 2 [205] e la cardiopatia ischemica [206]. In particolare, il CoQ10 ha migliorato la funzione endoteliale in pazienti con malattia coronarica al pari dell'esercizio fisico aerobico. ...
... I due trial effettuati su pazienti con cardiopatia ischemica del tipo angina stabile [206,220] concordano nell'affermare che la supplementazione di 8 settimane con 300 mg giornalieri di CoQ10 migliorano di pari passo la FMD dell'arteria brachiale e la funzione bioenergetica mitocondriale, dimostrando l'importante ruolo di quest'ultima nell'omeostasi endoteliale. Il gruppo di Tiano, inoltre, ha dimostrato sugli stessi pazienti un aumento dei livelli di espressione dell'enzima ecSOD che, proteggendo l'NO dall'ossidazione a perossinitrito, lo rende più disponibile ad esercitare la sua azione protettiva nei confronti dell'endotelio. ...
... Endothelial dysfunction plays a key role in the development, progression, and clinical manifestations of atherosclerosis and CVD. The effect of oral CoQ 10 supplementation on endothelial function in patients with coronary artery disease, diabetes mellitus or in elderly people has been investigated by several studies (Gao et al., 2011;Tiano et al., 2007;Watts et al., 2002). ...
... Endothelial function, measured by flow-mediated dilation (FMD) or nitroglycerin-mediated dilation (NMD), and the extracellular superoxide dismutase activity, improved in most of the subjects treated with CoQ 10 likely due to its antioxidant and anti-inflammatory activity (Yubero-Serrano et al., 2012), with a decrease in the rate of inactivation of NO to peroxynitrite by superoxide radicals. CoQ 10 may reduce the levels of these radicals under oxidative stress conditions (Gonzalez-Guardia et al., 2015;Tiano et al., 2007). In vitro studies have shown that CoQ 10 can efficiently prevent high glucose-induced endothelial cell apoptosis and adhesion to monocytes, which are relevant to the pathogenesis of atherosclerosis (Tsuneki et al., 2007). ...
Article
Coenzyme Q10 (CoQ10) is a ubiquitous molecule present in all eukaryotic organisms whose principal role in the cell is related to its participation in the electron transport chain in the inner mitochondrial membrane. CoQ10 plays a major role in the control of cell redox status, and both the amount and functionality of this molecule have been related to the regulation of reactive oxygen species generation. Numerous reports can be found discussing the implications of CoQ10 supplementation in human studies and clinical trials related to aging. However, few reviews have made an updating through the translational point of view to integrate both basic and clinical aspects. The aim of this paper is to review our current knowledge from CoQ10 implications at biochemical and physiological level, in order to unravel the molecular mechanisms involved in its application in clinical practice. Although the importance of CoQ10 has been mainly attributed to its role as an agent for energy transduction in mitochondria, new functions for CoQ10 have been described in the recent past years, including anti-inflammatory effects, gene expression regulation and lipid bilayer membranes stabilization, which explain its involvement in aging and age-related diseases such as cardiovascular diseases, renal failure and neurodegenerative diseases.
... A study was conducted in which patients with coronary artery disease (CAD) to determine the effect of CoQ 10 oral administration in dose 100 mg of the endothelium-dependent vasodilatation activity of extracellular superoxide dismutase (ecSOD). The results demonstrated that in CoQ 10 treated group in comparison with placebo group: ecSOD, endothelium-dependent relaxation was statistically higher [37]. ...
Article
The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation.
... SOD converts free superoxide radicals (O 2-) into hydrogen peroxide (H2O2), which is converted into oxygen (O2) and water (H2O). Moreover, the activity of extracellular superoxide dismutase (SOD3) and endothelium-dependent vasodilation are remarkably improved by CoQ10 supplementation [88]. In hypercholesterolemia, it was found that treatment with CoQ10 suppressed the oxidized low-density lipoprotein (oxLDL)-induced down-regulation of endothelial nitric oxide synthase (eNOS) and upregulation of inducible nitric oxide synthase (iNOS). ...
Article
Full-text available
Many neurodegenerative diseases share the same pathophysiology and etiologies, this led us to search for a product that may fit in the treatment of most of diseases, including neurological, cardiovascular, cancers, etc. Coenzyme Q10 is a natural product found in many kinds of beings like fish, beef, organ meat (liver, heart), whole grains, etc. Many studies on different animal models have concluded that coenzyme Q10 has neuroprotective effects against neurological disorders, improves mitochondrial functions, prevents oxidative stress and cellular death, stimulates cell growth, inhibits inflammation, and enhances neurogenesis. In addition, it decreases cerebral infarct size, inhibits platelet aggregation and blood thrombosis, and improves endothelial dysfunction. Coenzyme Q10 has important roles in different body systems ranging from cardioprotection, hepatoprotection, gastroprotection and nephroprotection to a documented function in slowing the aging processes. This article aims to summarize and discuss up-to-date experimental findings related to the mechanisms by which coenzyme Q10 and its analogs assist in treatment and thus improvement of many conditions in animals and human.
... We have found that statins increased plasma GSH enzyme activity by 16 %, the addition of coenzyme Q10 at 100 mg/d further increased the activity of plasma GSH activity by8.5 %.However, Lee BJ, Huang YC et al. showed that coenzyme Q10 at a dose of 150 mg/d increased the activity of SOD by 22.2% and of CAT by 4.5%, but had no effect on that of Plasma GSH activity [31]. Tiano et al. [32] administered coenzyme Q10 (300 mg/d) to patients with ischemic heart disease for 1 month, and they observed that those patients' extracellular superoxide dismutase activity and endothelium-dependent vasodilatation were improved after supplementation. Coenzyme Q10 supplementation at 300 mg/ day significantly enhanced antioxidant enzymes activities and lowered inflammation in a study by Lee BJ et al [33]. ...
Article
Full-text available
Background: Oxidative stress is one of the most potent inductors of endothelial dysfunction and is involved at all stages of atherosclerotic plaque evolution. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. Statins also possess direct free radical scavenging activity. However, the prooxidant effect of statins has also been reported as statins block the mevalonate pathway and the synthesis coenzyme Q10. This Additional Coenzyme Q10 depletion by statins in patients with coronary artery disease (CAD) may be a critical issue as it may reduce absolute benefits of statins. Objectives: The purpose of this study was to investigate the effects of high dose statins on plasma Malondialdehyde (MDA) levels and plasma glutathione levels in CAD patients who underwent recent PCI and to study whether addition of coenzyme Q10 (100 mg/d) has any additional effect on plasma Malondialdehyde (MDA) levels and plasma glutathione levels in patients already receiving high dose statin therapy. Methods: Twenty-one consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) in Department of Cardiology at our institute were studied. The cases (n = 21) were given high dose statins for first 1 week and then coenzyme Q10 (100 md /day) is added for next 1 week. Plasma Malondialdehyde(MDA) levels and plasma glutathione levels were analyzed at the time of admission before giving statins and at the end of 1 week of statin therapy and again after 1 week of Co-Q therapy. Results: Our results indicate that a relation exists between high plasma Malondialdehyde (MDA) levels and low plasma glutathione levels with coronary artery disease. High dose statins decrease MDA levels and increase plasma glutathione levels, even though they decrease coenzyme q levels in the body. It was also shown that addition of Coenzyme Q10 at 100 mg/d enhances plasma glutathione levels and decreases plasma MDA level still further in patients who have CAD, already receiving high dose statin therapy. Conclusions: Addition of Coenzyme Q10 at 100 mg/d has an additive effect with high dose statins in decreasing oxidative stress. Particularly in light of the excellent tolerance and affordability of this natural physiological compound, supplemental Coenzyme Q10 may emerge as an attractive option in future, and merits evaluation in additional large studies.
... Oral CoQ10 supplementation has been shown to ameliorate cardiac contractility and endothelial dysfunction in coronary heart failure patients [43]. CoQ10 also improves endothelium-dependent relaxation and endothelium-bound extracellular superoxide dismutase (ecSOD) activity by counteracting the rate of nitric oxide to peroxynitrite by superoxide anions [44]. A meta-analysis of randomized controlled trials also quantified the effect of CoQ10 on the endothelial function which was found beneficial in patients with endothelial dysfunction [45]. ...
... The study conducted by Tiano et al. evaluates the effect of Coenzyme Q10 administration among CAD patients by measuring endothelium-dependent vasodilatation one month after CABG. The study resulted that Coenzyme Q10 supplementation of 100 mg, three times daily, can increase the effects of extracellular superoxide dismutase (eSOD) [22]. Extracellular SOD can reduce oxidative damage by catalyzing superoxide-dismutase to oxygen and hydrogen peroxide. ...
Reperfusion arrhythmia following cardiac surgery has long been studied as part of myocardial damage. Reperfusion injury is thought to be exacerbated by oxygen-free radicals, whereas arrhythmogenic oscillations in membrane potential are mediated by reactive oxygen. Coenzyme Q10 is a lipid-soluble antioxidant that inhibits lipid peroxidation in biological membranes and supplies ATP cell synthesis, required as the organism’s primary energy source. This process explains how Coenzyme Q10 helps stabilize membranes and avoids critical metabolite depletion that may relate to reperfusion arrhythmia. There is a reduction of iatrogenic Coenzyme Q10 after coronary artery bypass surgery (CABG). On the other hand, there is an increased inflammatory process and cellular demand post CABG procedure. It leads to ischemia that can be manifested as arrhythmia. Reperfusion arrhythmia was less common in patients who took Coenzyme Q10. These findings suggest that Coenzyme Q10 supplementation might help patients with heart surgery avoid reperfusion arrhythmia. However, a higher-quality randomized controlled study is needed to determine the effect of Coenzyme Q10 in preventing reperfusion arrhythmia in cardiac surgery patients.
... Oral CoQ10 supplementation has been shown to ameliorate cardiac contractility and endothelial dysfunction in coronary heart failure patients [43]. CoQ10 also improves endothelium-dependent relaxation and endothelium-bound extracellular superoxide dismutase (ecSOD) activity by counteracting the rate of nitric oxide to peroxynitrite by superoxide anions [44]. A meta-analysis of randomized controlled trials also quantified the effect of CoQ10 on the endothelial function which was found beneficial in patients with endothelial dysfunction [45]. ...
Article
Background: Recurrent Miscarriage (RM) is one of the most frustrating clinical situations wherein most of the cases, neither the engaged obstetrician nor suffering couples know the exact etiology and cause of the disease. About 10-15% of women with RM diagnosed with antiphospholipid syndrome (APS) are characterized by the marked presence of antiphospholipid antibodies (aPLa). There are several scientific reports available on the association between APS and RM; however, scanty data available about the beneficial role of coenzyme Q10 (CoQ10) in APS and APS mediated RM. In the present attempt, we tried to gather information to explain the possible associations between the role of CoQ10 in RM and APS. Methods: We collected peer-reviewed literature using keywords; antiphospholipid syndrome, CoQ10, endothelial dysfunction, oxidative stress and recurrent miscarriage in online electronic databases, such as Web of Science, Science Direct, Google Scholar, PubMed and Medline. The qualitative analysis of content was done by summarizing interventions and findings of included studies, on the basis of which a conceptual framework was prepared for this narrative review. Results: The beneficial role of CoQ10 in diverse pathological conditions has been summarized and the evidence suggests that CoQ10 being a potent antioxidant helps in the amelioration of free radicalmediated aPLa production, endothelial damage and mitochondrial dysfunction. The supplementation of CoQ10 overcomes the immune dysregulation in idiopathic RM and APS; thus could be a possible therapeutic adjunct in such diseases. Conclusion: Based on this review, further comprehensive studies may be conducted to illuminate the beneficial therapeutic effects of supplementing CoQ10 on possible modifiable pathways involved in the progression of RM and APS.
... SOD converts free superoxide radicals (O 2-) into hydrogen peroxide (H2O2), which is converted into oxygen (O2) and water (H2O). Moreover, the activity of extracellular superoxide dismutase (SOD3) and endothelium-dependent vasodilation are remarkably improved by CoQ10 supplementation [88]. In hypercholesterolemia, it was found that treatment with CoQ10 suppressed the oxidized low-density lipoprotein (oxLDL)-induced down-regulation of endothelial nitric oxide synthase (eNOS) and upregulation of inducible nitric oxide synthase (iNOS). ...
Article
Full-text available
Many neurodegenerative diseases share the same pathophysiology and etiologies, this led us to search for a product that may fit in the treatment of most of diseases, including neurological, cardiovascular, cancers, etc. Coenzyme Q10 is a natural product found in many kinds of beings like fish, beef, organ meat (liver, heart), whole grains, etc. Many studies on different animal models have concluded that coenzyme Q10 has neuroprotective effects against neurological disorders, improves mitochondrial functions, prevents oxidative stress and cellular death, stimulates cell growth, inhibits inflammation, and enhances neurogenesis. In addition, it decreases cerebral infarct size, inhibits platelet aggregation and blood thrombosis, and improves endothelial dysfunction. Coenzyme Q10 has important roles in different body systems ranging from cardioprotection, hepatoprotection, gastroprotection and nephroprotection to a documented function in slowing the aging processes. This article aims to summarize and discuss up-to-date experimental findings related to the mechanisms by which coenzyme Q10 and its analogs assist in treatment and thus improvement of many conditions in animals and human.
... According to previous investigations that have reported endurance athletes may during periods of intense training consequent to high levels of oxidative metabolic stress that may incur low plasma CoQ10 levels in athletes and subsequent increased blood metabolites levels (Weston, Zhou, Weatherby, & Robson, 1997). Also, the lack of cohesive sport studies on the effect CoQ10 on improvement of blood lipid level, muscle damage and lactate, and majority of studies have been on disease populations and animals (Colquhoun et al., 2005;Lee et al., 2012;Singh et al., 2000;Singh et al., 1998;Tiano et al., 2007;Yuvaraj, Premkumar, Vijayasarathy, Gangadaran, & Sachdanandam, 2008) were the reasons of present study. So, the aim of present study was to investigate the impact of 14 days CoQ10 supplementation on lipid profiles and muscle damage subsequent two weeks intense aerobic training. ...
... 99 In this context, CoQ10 has recently been shown to be effective in enhancing endothelial functionality in patients with coronary disease by counteracting nitric oxide oxidation. 100 Several controlled trials in patients with ischemic heart disease showed significant improvement in exercise tolerance, reduction of ST-segment depression and angina, with no alteration in heart rate or blood pressure. 101,102 As for most metabolic agents, also CoQ10 could be particularly effective in patients with heart failure, as recently shown in a double-blind, placebo-controlled cross-over study. ...
Article
Coronary artery disease (CAD) is a major cause of morbidity and mortality in the world. Therapy for stable CAD is currently based on conventional medical therapy, including nitrates, β-blockers and calcium-channels antagonists and, more recently, metabolic therapy, of which a pivotal therapeutic role is increasingly recognized. Under normoxic condition, the healthy heart derives 2/3 of its energy from the free fatty acid (FFA) pathway, the other source of energy being derived from glucose oxidation. However, glycolysis requires less O2 per mole of ATP generated compared with FFA oxidation. On this basis, shifting energy substrate utilization from fatty acid metabolism to glucose metabolism can be more efficient in terms of ATP production per mole of oxygen utilized. A number of different approaches have been used to manipulate energy metabolism in the heart. These approaches include direct agents, such as dichloroacetate, L-carnitine, ribose or lipoic acid which directly increase glucose oxidation, or indirect methods, through the inhibition of free fatty acids oxidation. Among these, the most important are carnitil-palmitoyl-transpherase I (CPT-I) inhibitors, which inhibit FFA mitochondrial uptake (e.g. etomoxir, perhexiline, oxphenicine), or 3-ketoacyl-coenzyme-A thiolase (3-KAT) inhibitors, such as trimetazidine, which inhibits the last enzyme involved in β-oxidation. In most patients with ischemic heart disease metabolic abnormali- ties, if not adequately treated, will heavily contribute to the occurrence of complications, of whom severe left ventricular dysfunction is at present one of the most frequent and insidious. In this paper, all possible metabolic approaches to ischemic heart disease are reviewed and discussed.
... The protective activity of coenzyme Q 10 towards endothelial cells against the background of oxidative stress can also be related to its ability to control the activity of endothelial and inducible NO • synthases providing the optimum (nontoxic) level of NO • (Tsai et al., 2012). The possibility of correction of endothelial dysfunction by coenzyme Q 10 was demonstrated in previous experiments with human endothelial cells in vitro (Tsuneki et al., 2013), with rat aortic rings ex vivo (Lonnrot et al., 1998) as well as in populational (Gao et al., 2012) and clinical studies in patients with ischemic heart disease (Tiano et al., 2007;Dai et al., 2011) and type II diabetes (Hamilton et al., 2009) receiving long-term per os treatment with coenzyme Q 10 . ...
Article
This study examined whether coenzyme Q10 can improve nitric oxide (NO)-dependent vasodilatation in the rat aorta after pre-incubation or intravenous administration. In initial experiments, intact isolated aortic rings were incubated with coenzyme Q10 or L-arginine. In further experiments, coenzyme Q10 was administered intravenously in anesthetized rats, then in 2h aorta was isolated. In both cases, after preliminary preparation the isolated aortic rings were tested for acetylcholine-induced NO-dependent relaxation. Acetylcholine elicited concentration-dependent relaxation of phenylephine precontracted aortic rings. Relaxant responses to acetylcholine were markedly potentiated after pre-incubation with coenzyme Q10 or L-arginine. The maximum relaxant responses (%) were significantly increased from 64.1±5.3 (control) to 89.8±3.0 and 83.6±3.0 (coenzyme Q10 and L-arginine, respectively). pD2 (-lgEC50) value in control study was 5.81±0.28, after pretreatment with coenzyme Q10 or L-arginine were 7.59±0.16 and 7.26±0.32, respectively. There was no difference between coenzyme Q10 and L-arginine groups. After intravenous administration, the relaxant responses to acetylcholine were significantly increased in coenzyme Q10-treated group (94.2±2.0) compared with controls (68.1±4.4). pD2 values were also different between control and treatment groups (5.79±0.29 vs. 8.14±0.65, respectively).
... In patients with CAD, the activity of endothelium-bound ecSOD is severely reduced resulting in decreased vasodilation [16]. A clinical study has demonstrated that 1 month supplementation of 300 mg/day significantly improved endothelium dependent vasodilation and increased levels of ecSOD which is attributed to the capability of CoQ10 by counteracting NO inactivation [17]. ...
Article
Full-text available
This systematic review is aimed to identify, evaluate and summarize the role of oral Coenzyme Q10 supplementation in prevention and treatment of cardiovascular diseases (CVD). CoQ10 is concentrated primarily in the cellular mitochondria where it functions as a co-factor transferring electrons from Complex I to Complex II, III ultimately resulting in the formation of energy in the form of ATP. Coenzyme Q10 an endogenous antioxidant declines in our body because of various factors like aging, diseases and use of certain drugs like statins, beta-blockers which exacerbate its deficiency. Deficiency of this important endogenous antioxidant CoQ10 results in energy depleted state. Published data and research have suggested that Coenzyme Q10 an endogenous antioxidant has a potential for being used in the prevention and treatment of CVDs, in particular in Heart failure and Ischemic heart disease. Supplementation with CoQ10 not only corrects the deficiency of CoQ10 by improving the circulating levels of CoQ10 but also shows a significant improvement in various parameters like ejection fraction, NYHA class, symptom score and survival rate. Being a natural substance with low toxicity.
... Blood and tissue levels of CoQ 10 are depleted in congestive heart failure (Boreková et al., 2008) and across a range of cardiovascular conditions. Numerous beneficial effects of CoQ 10 administration have been observed, including an improvement in symptoms and a reduction in mortality in heart failure (Mortensen et al., 2014), decreases to myocardial thickness (Langsjoen et al., 1993;Adarsh et al., 2008), reduction in hypertension (Rosenfeldt et al., 2007) improvement in cardiac contractility and amelioration of endothelial dysfunction (Tiano et al., 2007) and improved exercise performance (Cooke et al., 2008;Deichmann et al., 2012). In patients with ischemeic left ventricular systolic dysfunction, 8 weeks supplementation with 300 mg daily CoQ 10 was found to improve mitochondrial function and flow-mediated dilatation; and the improvement of flow-mediated dilatation correlated with the change in mitochondrial function, suggesting that CoQ 10 improved endothelial function via reversal of mitochondrial dysfunction (Dai et al., 2011). ...
Article
Full-text available
Introduction: With an aging population there is an important need for the development of effective treatments for the amelioration of cognitive decline. Multiple mechanisms underlie age-related cognitive decline including cerebrovascular disease, oxidative stress, reduced antioxidant capacity and mitochondrial dysfunction. CoQ10 is a novel treatment which has the potential to improve brain function in healthy elderly populations due to established beneficial effects on mitochondrial function, vascular function and oxidative stress.Methods and Analysis: We describe the protocol for a 90-day randomized controlled trial which examines the efficacy of Ubiquinol (200 mg/day) vs. placebo for the amelioration of cognitive decline in a healthy (non-demented) elderly sample, aged 60 years and over. The primary outcome is the effect of Ubiquinol at 90 days compared to baseline on CogTrack composite measures of cognition. Additional cognitive measures, as well as measures of cardiovascular function, oxidative stress, liver function and mood will also be monitored across 30-, 60- and 90- day time points. Data analyses will involve repeated measures analysis of variance (ANOVA).Discussion: This study will be the first of its kind to provide important clinical and mechanistic data regarding the efficacy of Ubiquinol as a treatment for age-related cognitive decline in the healthy elderly with important implications for productivity and quality of life within this age group.Clinical Trial Registration: The trial has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTRN12618001841268).
... SOD converts free superoxide radicals (O 2-) into hydrogen peroxide (H2O2), which is converted into oxygen (O2) and water (H2O). Moreover, the activity of extracellular superoxide dismutase (SOD3) and endothelium-dependent vasodilation are remarkably improved by CoQ10 supplementation [88]. In hypercholesterolemia, it was found that treatment with CoQ10 suppressed the oxidized low-density lipoprotein (oxLDL)-induced down-regulation of endothelial nitric oxide synthase (eNOS) and upregulation of inducible nitric oxide synthase (iNOS). ...
Article
Full-text available
Many neurodegenerative diseases share the same pathophysiology and etiologies, this led us to search for a product that may fit in the treatment of most of diseases, including neurological, cardiovascular, cancers, etc. Coenzyme Q10 is a natural product found in many kinds of beings like fish, beef, organ meat (liver, heart), whole grains, etc. Many studies on different animal models have concluded that coenzyme Q10 has neuroprotective effects against neurological disorders, improves mitochondrial functions, prevents oxidative stress and cellular death, stimulates cell growth, inhibits inflammation, and enhances neurogenesis. In addition, it decreases cerebral infarct size, inhibits platelet aggregation and blood thrombosis, and improves endothelial dysfunction. Coenzyme Q10 has important roles in different body systems ranging from cardioprotection, hepatoprotection, gastroprotection and nephroprotection to a documented function in slowing the aging processes. This article aims to summarize and discuss up-to-date experimental findings related to the mechanisms by which coenzyme Q10 and its analogs assist in treatment and thus improvement of many conditions in animals and human.
... SOD converts free superoxide radicals (O 2-) into hydrogen peroxide (H2O2), which is converted into oxygen (O2) and water (H2O). Moreover, the activity of extracellular superoxide dismutase (SOD3) and endothelium-dependent vasodilation are remarkably improved by CoQ10 supplementation [88]. In hypercholesterolemia, it was found that treatment with CoQ10 suppressed the oxidized low-density lipoprotein (oxLDL)-induced down-regulation of endothelial nitric oxide synthase (eNOS) and upregulation of inducible nitric oxide synthase (iNOS). ...
Article
Vitamin C (Ascorbic acid) is a water-soluble vitamin and is highly polar compound. Humans have to get what they need of Vitamin C from food, including citrus fruits, broccoli, and tomatoes. Human bodies require vitamin C for the growth and repair of tissues in all parts of the body. Vitamin C is one of many antioxidants that block some of the damage caused by free radicals. There are some thoughts that vitamin C might help the heart and the blood vessels by preventing clots in veins and arteries, high blood pressure, and high cholesterol. Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. This mini review will focus on the role of vitamin C in these major symptoms.
... The mechanisms underpinning such positive effects are multiple and include the suppression of lymphocytic infiltration, decreased endothelial cell oxidative stress (Tiano et al., 2007), and upregulation of eNOS and downregulation of iNOS, NF-κB and PICs (Huo et al., 2018;Tsai et al., 2012). ...
Article
Activated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways and consequent mitochondrial aberrations are involved in the pathophysiology of psychiatric disorders including major depression, bipolar disorder and schizophrenia. They offer independent and shared contributions to pathways underpinning medical comorbidities including insulin resistance, metabolic syndrome, obesity and cardiovascular disease - herein conceptualized as somatoprogression. This narrative review of human studies aims to summarize relationships between IO&NS pathways, neuroprogression and somatoprogression. Activated IO&NS pathways, implicated in the neuroprogression of psychiatric disorders, affect the pathogenesis of comorbidities including insulin resistance, dyslipidaemia, obesity and hypertension, and by inference, metabolic syndrome. These conditions activate IO&NS pathways, exacerbating neuroprogression in psychiatric disorders. The processes whereby proinflammatory cytokines, nitrosative and endoplasmic reticulum stress, NADPH oxidase isoforms, PPARγ inactivation, SIRT1 deficiency and intracellular signalling pathways impact lipid metabolism and storage are considered. Through associations between body mass index, chronic neuroinflammation and FTO expression, activation of IO&NS pathways arising from somatoprogression may contribute to neuroprogression. Early evidence highlights the potential of adjuvants targeting IO&NS pathways for treating somatoprogression and neuroprogression.
... Smanio et al. showed that CPEX is better than routine ECG stress testing in this cohort, but inferior to MPI [25]. Furthermore, CPEX has shown to be useful in assessing new medical therapies for coronary artery disease [26]. However, it was Belardinelli et al. who delivered a convincing case for CPEX with two landmark papers. ...
... CoQ10 supplementation has beneficial effects on endothelial function [425] which might contribute to functional improvements in patients with cardiovascular diseases. CoQ10 supplementation (300 mg/day for 1 month) in patients with coronary heart disease resulted in improvements in VO 2 max as well as endothelialdependent vasodilation and endothelium-bound extracellular SOD activity [282]. CoQ10 (100 mg/day for 1 month) improved VO 2 peak and endothelium-dependent dilation of the brachial artery in patients with chronic heart failure, particularly when combined with regular exercise training [283]. ...
Article
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Antioxidant supplements are commonly consumed by endurance athletes to minimize exercise-induced oxidative stress, with the intention of enhancing recovery and improving performance. There are numerous commercially available nutritional supplements that are targeted to athletes and health enthusiasts that allegedly possess antioxidant properties. However, most of these compounds are poorly investigated with respect to their in vivo redox activity and efficacy in humans. Therefore, this review will firstly provide a background to endurance exercise-related redox signalling and the subsequent adaptations in skeletal muscle and vascular function. The review will then discuss commonly available compounds with purported antioxidant effects for use by athletes. N-acetyl cysteine may be of benefit over the days prior to an endurance event; while chronic intake of combined 1000 mg vitamin C + vitamin E is not recommended during periods of heavy training associated with adaptations in skeletal muscle. Melatonin, vitamin E and α-lipoic acid appear effective at decreasing markers of exercise-induced oxidative stress. However, evidence on their effects on endurance performance are either lacking or not supportive. Catechins, anthocyanins, coenzyme Q10 and vitamin C may improve vascular function, however, evidence is either limited to specific sub-populations and/or does not translate to improved performance. Finally, additional research should clarify the potential benefits of curcumin in improving muscle recovery post intensive exercise; and the potential hampering effects of astaxanthin, selenium and vitamin A on skeletal muscle adaptations to endurance training. Overall, we highlight the lack of supportive evidence for most antioxidant compounds to recommend to athletes.
... In this context, consistent with our results, CoQ10 application in patients undergoing hemodialysis was effective in improvement of serum levels of OTS biomarkers [60,61]. Lee et al. and Tiano et al. also documented that 300 mg/day of CoQ10 supplementation significantly increased antioxidant enzymes activities in people who had coronary artery disease (CAD) [62,63]. In similar studies, ameliorative effects of CoQ10 supplementation on oxidative stress parameters in patients with other pathologic conditions, such as relapsing-remitting multiple sclerosis and fibromyalgia have been reported [33,64]. ...
Article
Full-text available
Bipolar disorder (BPD) is a severe and chronic mental disease with high rates of social and functional disability. To explain the emergence and maintenance of BPD, increasing attention has been focused on dimensions of inflammation and oxidative stress (OTS). Coenzyme Q10 (CoQ10) is known for its anti-oxidant and anti-inflammatory effects; accordingly, the aim of the present study was to investigate, if compared to placebo, adjuvant CoQ10 might favorably impact on serum levels of inflammatory and OTS biomarkers in patients with BPD during their depressive phase. A total of 89 BPD patients, currently in a depressive episode were allocated by block randomization either to the adjuvant CoQ10 (200 mg/day) condition or to the placebo condition. At baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interlukin-6 (IL-6), and IL-10 were assessed. 69 patients completed the 8-week lasting study. Compared to baseline and to the placebo condition, serum levels of TTG and TAC significantly increased, and TNF-α, IL-10, and NO statistically decreased over time in the adjuvant CoQ10 condition. No statistically significant changes were observed for CAT, MDA, and IL-6. The pattern of results suggests that compared to placebo and over a time lapse of 8 weeks, adjuvant CoQ10 favorably impacted on OTS and inflammatory biomarkers in patients with BPD during the depressive episode. Thus, CoQ10 might be considered a safe and effective strategy for treatment of patients with BPD during their depressive phase.
... The results of our systematic review and meta-analysis demonstrate that CoQ10 supplementation significantly increases SOD activity. There are no similar systematic reviews about the effect of CoQ10 on SOD activity, but several RCTs indicated that CoQ10 supplementation can increase the SOD activity [28,53,60]. It has been accepted that SOD is one of the major detoxifying enzymes in the mitochondria [61]. ...
Article
Full-text available
PurposeOxidative stress (OS) is associated with several chronic complications and diseases. The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown to be beneficial. However, the impact of CoQ10 as a preventive agent against OS has not been systematically investigated.MethodsA systematic literature search was performed using the PubMed, SCOPUS, EMBASE, and Cochrane Library databases to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model.ResultsSeventeen randomized clinical trials met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD − 0.94; 95% CI − 1.46, − 0.41; I2 = 87.7%) and a significant increase in total antioxidant capacity (TAC) (SMD 0.67; 95% CI 0.28, 1.07; I2 = 74.9%) and superoxide dismutase (SOD) activity (SMD 0.40; 95% CI 1.12, 0.67; I2 = 9.6%). The meta-analysis found no statistically significant impact of CoQ10 supplementation on nitric oxide (NO) (SMD − 1.40; 95% CI − 0.12, 1.93; I2 = 92.6%), glutathione (GSH) levels (SMD 0.41; 95% CI − 0.09, 0.91; I2 = 70.0%), catalase (CAT) activity (SMD 0.36; 95% CI − 0.46, 1.18; I2 = 90.0%), or glutathione peroxidase (GPx) activities (SMD − 1.40; 95% CI: − 0.12, 1.93; I2 = 92.6%).Conclusion CoQ10 supplementation, in the tested range of doses, was shown to reduce MDA concentrations, and increase TAC and antioxidant defense system enzymes. However, there were no significant effects of CoQ10 on NO, GSH concentrations, or CAT activity.
Article
Background Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. Methods Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow‐mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA), and 8‐hydroxydeoxyguanosine (8‐OHdG) levels were measured. The potential confounders identified by univariate analyses (p < 0.15) were selected in a stepwise multiple regression model. Results In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/ml, and endothelial dysfunction was prevalent (91.0%) using a cut‐off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, p < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (β = 0.018, p < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/ml), the conclusion remained unchanged (β = 0.584, p < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = −0.48, p < 0.001) and 8‐OHdG (r = −0.43, p < 0.001) levels. Conclusions Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients. This article is protected by copyright. All rights reserved.
Article
Coenzyme Q10 (CoQ10) is a natural antioxidant compound that prevents the vascular damage induced by free radicals and the activation of inflammatory signaling pathways. Supplementation with CoQ10 is safe though its bioavailability is generally low, as far as variable depending on the pharmaceutical form of preparation. Recently, the development of phytosome technology has improved the bioavailability of CoQ10 and definitely facilitated its effective use in clinical practice. The present double‐blind, randomized, placebo‐controlled, crossover clinical study aimed to investigate the effect on endothelial reactivity and total antioxidant capacity (TAC) of either acute and chronic supplementation with CoQ10 phytosome in a sample of 20 healthy young nonsmoking subjects. CoQ10 phytosome supplementation acutely improved endothelial reactivity in comparison with baseline and placebo (+4.7% ± 0.9% vs. −0.1 %± 0.3% p < 0.05). Middle‐term supplementation of the tested pharmaceutical formulation of CoQ10 significantly improved mean arterial pressure (−2.2 ± 1.1 mmHg vs. 0.2 ± 0.7 mmHg, p < 0.05 vs. placebo) and TAC (+29.6% ± 3.2% vs. +1.9% ± 0.8%, p < 0.05 vs. placebo). Endothelial reactivity improved compared with baseline following middle‐term dietary supplementation with CoQ10 phytosome (+5.7% ± 1.1%, p < 0.05).
Chapter
Human coenzyme Q (CoQ10) or ubiquinone is mainly known for its bioenergetic role as a proton and electron carrier in the inner mitochondrial membrane and is also an endogenous lipophilic antioxidant, ubiquitous in biological membranes. It is also present in plasma lipoproteins, where it plays a well-recognized antioxidant role. More recently coenzyme Q10 was also shown to affect gene expression by modulating the intracellular redox status. Its involvement in many cellular and extracellular functions suggests that its use as a food supplement could be beneficial in conditions associated with increased oxidative stress underlying different pathological conditions. In reproductive biology, CoQ10 has been shown to play a role in fertility of both males and females.
Article
Cardiovascular diseases (CVD) affect 1 in 3 adults and remain the leading causes of death in America. Advancing age is the major risk factor for CVD. Recent plateaus in CVD-related mortality rates in high income countries after decades of decline highlight a critical need to identify novel therapeutic targets and strategies to mitigate and manage the risk of CVD development and progression. Vascular dysfunction, characterized by endothelial dysfunction and large elastic artery stiffening, is independently associated with an increased CVD risk and incidence and is therefore an attractive target for CVD prevention and management. Vascular mitochondria have emerged as an important player in maintaining vascular homeostasis. As such, age and disease related impairments in mitochondrial function contribute to vascular dysfunction and consequent increases in CVD risk. This review outlines the role of mitochondria in vascular function and discusses the ramifications of mitochondrial dysfunction on vascular health in the setting of age and disease. The adverse vascular consequences of increased mitochondria derived reactive oxygen species, impaired mitochondrial quality control and defective mitochondrial calcium cycling are emphasized, in particular. Current evidence for both lifestyle and pharmaceutical mitochondrial-targeted strategies to improve vascular function is also presented.
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The regular exercise training is so effective for improvement of health. However, there is evidence that intense aerobic training may cause damage to the tissues with different ways. Scientists of sport science are used various supplements for prevention this deleterious effects which CoQ10 (coenzymeQ10) is one of these supplements. This study was designed to investigate the effects of short-term CoQ10 supplementation on serum lipid profile and indirect muscle damage indices levels subsequence of one session intense aerobic training in cyclists. The research studied on healthy elite men cyclists to assess the efficacy of short-term CoQ10 supplementation. Cyclists were divided into 2 groups (each group 7; age range 19- 25 years) to receive CoQ10 and dextrose. Blood samples were collected during 2 weeks of prepare camp, 2 d before the training camp (baseline), 18-24 hrs after supplementation and training session of the first and last training session and in order to assess serum levels of triglycerides high-density lipoprotein has been used autoanalyzer. Also, aforementioned method was used to calculate Creatine kinase and lactate dehydrogenase activity. Fourteen cyclists completed the course of the study. Serum lipid levels in the consumer CoQ10 compare placebo group decreased following one session aerobic training (P<.05). However, baseline lipid levels were unchanged (P>.05) except triglyceride which had descending procedure (from 72.7±17.9 to 51.9±11.9) in CoQ10 group (P<.001). Ascending response of indirect muscle damage indices (Creatine kinase and lactate dehydrogenase) and capillary lactate decreased in the CoQ10 group compare to placebo group (301±45.11 versus 340.42±36.41, 362.71±32.58 versus 407.14±60.9 and 1.04±0.24 versus 1.24±0.19 for every index, respectively) in subsequent last session of aerobic training (P<.05). The present study showed that short-term supplementation with CoQ10 could insignificantly reduce serum levels of some lipid profiles and significantly reduce muscle damage in healthy elite cyclists.
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Coenzyme Q10 (CoQ10), a strong antioxidant, is used extensively in food, cosmetic and medicine industries. A natural producer, Rhodopseudomonas palustris (R. palustris), was engineered to overproduce CoQ10. For increasing the CoQ10 content, crtB gene was deleted to block the carotenoid pathway. crtB gene deletion led to 33% improvement of CoQ10 content over the wild type strain. However, it was found that the yield of hopanoids was also increased by competing for the precursors from carotenoid pathway with CoQ10 pathway. To further increase the CoQ10 content, hopanoid pathway was blocked by deleting shc gene, resulting in R. palustris [Δshc, ΔcrtB] to produce 4.7 mg g‐1 DCW CoQ10, which was 1.2 times higher than the CoQ10 content in the wild type strain. The common strategy of co‐expression of rate‐limiting enzymes (DXS, DPS and UbiA) was combined with the pathway blocking method resulted in 8.2 mg g‐1 DCW of CoQ10, which was 2.9 times higher than that of wild type strain. The results suggested a synergistic effect among different metabolic engineering strategies. This study demonstrates the potential of R. palustris for CoQ10 production and provides viable strategies to increase CoQ10 titer.
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Coenzyme Q10 (CoQ10) is an essential component of the electron transport system and the only lipid-soluble compound synthesized endogenously present in all cell membranes with bioenergetics and antioxidant properties. AgingAging, neurodegenerative disorders, cardiovascular disease and other aged-related diseases, as well as genetic mutations, have been associated with CoQ10 deficiency. Since both limited uptake and low bioavailability of dietary CoQ10 might influence in this deficiency, supplementation with CoQ10 must be considered in those cases as therapeutic solution. However, more research is needed in order to identify the appropriate dose, the effectiveness and the bioavailability of orally-administered CoQ10. Furthermore research must be developed in order to design therapeutic agents to induce the endogenous synthesis CoQ10 specially in elderly people. This review will focus in the most relevant biochemical characteristics of this important antioxidantAntioxidants, including its main functions, levels and distribution in human organism and the therapeutic potential of CoQ10, especially, during agingAging and the associated diseases.
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Background Mitochondrial adenosine triphosphate (ATP) production requires a small electron carrier, co-enzyme Q10 (CoQ10), which has been used as adjunctive therapy in patients with cardiovascular disease (CVD) and hypertension because of its bioenergetics and antioxidant properties. Randomized controlled trials (RCTs) beyond the last two decades evaluating CoQ10 added to conventional therapy resulted in mixed results and were underpowered to address major clinical endpoints. Objectives The objective of this systematic review was to examine the impact of CoQ10 supplementation on older adults with CVD or hypertension in the last two decades (2000-2020). Methods PubMed/MEDLINE, Cochrane Database, CINAHL, and Google Scholar databases were searched systematically, as well as manual review of references from selected studies, to identify RCTs or cross-over studies evaluating the efficacy of CoQ10 supplementation. Data extracted from selected studies include trial design and duration, treatment, dose, participant characteristics, study variables, and important findings. Results A total of 14 studies (1067 participants) met the inclusion criteria. The effect of CoQ10 supplementation was examined among predominantly older adult males with heart failure (n = 6), hypertension (n = 4), ischemic heart disease (n = 3), and preoperatively in patients scheduled for cardiac surgery (n = 1). CoQ10 supplementation in patients with heart failure improved functional capacity, increased CoQ10 serum levels, and led to fewer major adverse cardiovascular events (MACE). CoQ10 had positive quantifiable effects on inflammatory markers in patients with ischemic heart disease. Myocardial hemodynamics improved in patients who received CoQ10 supplementation prior to cardiac surgery. Effects on hypertension were inconclusive. Conclusion In predominantly older adult males with CVD or hypertension, CoQ10 supplementation added to conventional therapy is safe and offers benefits clinically and at the cellular level. However, results of the trials need to be viewed with caution, and further studies are indicated before wide spread usage of CoQ10 is recommended in all older adults.
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Diabetes mellitus is a debilitating metabolic disorder in which oxidative stress plays a key role in the pathogenesis of the homeostatic regulation of glucose. Oxidative stress results from an imbalance between the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and defending antioxidant systems and has a major contribution in the pathogenesis of many diseases including diabetes. This has led to the promising idea that using antioxidants may be a useful therapeutic strategy. In this chapter we focus on the therapeutic role of some commonly used antioxidants including vitamin E, vitamin C, alpha-lipoic acid, l-carnitine, coenzyme Q10, and ruboxistaurin in the treatment of diabetes or its complications. We focus on the results from human clinical studies and summarize their key outcomes. Despite the promise of therapeutic benefits based on preclinical data, the results of large-scale clinical trial are inconclusive and suggest that the routine use of antioxidants may have limited or no therapeutic benefits.
Article
Coenzyme Q10 (CoQ) or ubiquinone is found in the biological system which is synthesized by the conjugation of benzoquinone ring with isoprenoid chain of variable length. Coenzyme Q10 supplementation energizes the body and increases body energy production in the form of ATP and helps to treat various human diseases such as cardiomyopathy, muscular dystrophy, periodontal disease, etc. Reports of these potential therapeutic advantages of CoQ10 have resulted in its high market demand, which focus the researchers to work on this molecule and develop better bioprocess methods for commercial level production. At the moment, chemical synthesis, semi-synthetic method as well as bio-production utilizing microbes as biofactory are in use for the synthesis of CoQ10. Chemical synthesis involves use of cheap and easily available precursor molecules such as isoprenol, chloromethylquinone, vinylalane, and solanesol. Chemical synthesis methods due to the use of various solvents and chemicals are less feasible, which limits its application. The microbial production of CoQ10 has added advantages of being produced in optically pure form with high yield using inexpensive medium composition. Several bacteria, e.g., Agrobacterium, Paracoccus, Rhodobacterium, and yeast such as Candida, Rhodotorula are the potent ubiquinone producer. Some alternative biosynthetic pathway for designing of CoQ10 production coupled with metabolic engineering might help to increase CoQ10 production. The most common practiced strategy for strain development for commercial CoQ10 production is through natural isolation and chemical mutagenesis. Here, we have reviewed the chemical, semi-synthetic as well as microbial CoQ10 production in detail.
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Exercise electrocardiography has low sensitivity for detection of myocardial ischemia. However, when combined with cardiopulmonary exercise testing (CPEX), the sensitivity and specificity of ischemia detection improves significantly. CPEX offers unique advantages over imaging techniques in tricky situations such as balanced ischemia. Early abnormal oxygen uptake would point toward profound coronary stenosis that could be missed in perfusion imaging. CPEX could be an invaluable tool in asymptomatic left bundle branch block pattern, without exposing patients to the risks of computerized tomography or invasive coronary angiography. Normal oxygen uptake curves would rule out significant coronary stenosis as the cause of left bundle branch block pattern. Elseways, abnormal oxygen uptake in patients with normal coronary arteries could indicate microvascular angina. Furthermore, exercise capacity is an excellent predictor of cardiovascular risk in those with and without heart disease. Using two clinical cases we introduce the concept of gas-exchange and hemodynamic changes encountered in ischemic heart disease.
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Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol levels and increased risk for premature cardiovascular disease. Here, we examined FH pathophysiology in skin fibroblasts derived from FH patients harbouring heterozygous mutations in the LDL-receptor. Fibroblasts from FH patients showed a reduced LDL-uptake associated with increased intracellular cholesterol levels and coenzyme Q10 (CoQ10) deficiency, suggesting dysregulation of the mevalonate pathway. Secondary CoQ10 deficiency was associated with mitochondrial depolarization and mitophagy activation in FH fibroblasts. Persistent mitophagy altered autophagy flux and induced inflammasome activation accompanied by increased production of cytokines by mutant cells. All the pathological alterations in FH fibroblasts were also reproduced in a human endothelial cell line by LDL-receptor gene silencing. Both increased intracellular cholesterol and mitochondrial dysfunction in FH fibroblasts were partially restored by CoQ10 supplementation. Dysregulated mevalonate pathway in FH, including increased expression of cholesterogenic enzymes and decreased expression of CoQ10 biosynthetic enzymes, was also corrected by CoQ10 treatment. Reduced CoQ10 content and mitochondrial dysfunction may play an important role in the pathophysiology of early atherosclerosis in FH. The diagnosis of CoQ10 deficiency and mitochondrial impairment in FH patients may also be important to establish early treatment with CoQ10. https://www.ncbi.nlm.nih.gov/pubmed/30292637
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The article describes the current understanding of the oxidative stress and its influence on the development of pregnancy complications: premature labor, preterm premature rupture of the membranes, preeclampsia, placental insufficiency, intrauterine growth restriction, congenital malformations. Particular attention is paid to the role of antioxidants in prophylaxis of pregnancy disorders and of a number of diseases in neonates. Vitamins and micronutrients supplementation may help restore balance to the oxidative pathways. The development of safe and efficient antioxidant strategies to prevent o minimize oxidative damage before and during pregnancy and during lactation are required.
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Suspended microbes gradually lost advantages in practical applications of PAHs and heavy metals bioremediation. Therefore this study investigated the effect of immobilization on phenanthrene degradation by Bacillus sp. P1 in the presence of different Cd(II) concentrations. Condensed Bacillus sp. P1 was immobilized with polyvinyl alcohol and sodium alginate and PVA-SA-cell cryogel beads were prepared. The results indicated that the use of gel beads increased the number of adsorption sites thus accelerating phenanthrene degradation. In addition, changes in detoxification indices, including superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), were determined to elucidate the immobilization mechanisms related to cells protection from Cd(II) when degrading phenanthrene. By protecting the gel membrane, oxidative damage was minimized, while SOD activity increased from 55.72 to 81.33 U/mgprot as Cd(II) increased from 0 to 200 mg/L but later dropped to 44.29 U/mgprot as Cd(II) increased to 300 mg/L for the non-immobilized system. On the other hand, the SOD activity kept increasing from 52.23 to 473.35 U/mgprot for the immobilized system exposed to Cd(II) concentration between 0 and 300 mg/L. For CAT and GSH, immobilization only slowed down the depletion process without any change on the variation trends. The changes in surface properties and physiological responses of microbes caused the differences of immobilization effect on phenanthrene biodegradation in the presence of Cd(II), which is a novel finding.
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Background Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. Objective We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). Methods In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400 mg/day or placebo for 3 months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). Results Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39–1.80], post-RHI 1.74 [IQR 1.63–2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53–1.85], post-RHI 1.51 [IQR 1.39–2.11], p = 0.198). Conclusions Ubiquinol 400 mg/day for 3 months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. Clinical Trial Registration Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.
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Heart failure (HF) is one of the most common causes of death in Western society. Recent results underscore the utility of coenzyme Q10 (CoQ10) addition to standard medications in order to reduce mortality and to improve quality of life and functional capacity in chronic heart failure (CHF). The rationale for CoQ10 supplementation in CHF is two-fold. One is the well-known role of CoQ10 in myocardial bioenergetics, and the second is its antioxidant property. Redox balance is also improved by oral supplementation of CoQ10, and this effect contributes to enhanced endothelium-dependent relaxation. Previous reports have shown that CoQ10 concentration is decreased in myocardial tissue in CHF and by statin therapy, and the greater the CoQ10 deficiency the more severe is the cardiocirculatory impairment. In patients with CHF and hypercholesterolaemia being treated with statins, the combination of CoQ10 with a statin may be useful for two reasons: decreasing skeletal muscle injury and improving myocardial function. Ubiquinol, the active reduced form of CoQ10, presents higher bioavailability than the oxidised form ubiquinone, and should be the preferred form to be added to a statin. The combination ezetimibe/simvastatin may have advantages over single statins. Since ezetimibe reduces absorption of cholesterol and does not affect CoQ10 synthesis in the liver, the impact of this combination on CoQ10 tissue levels will be much less than that of high dose statin monotherapy at any target low density lipoprotein-cholesterol (LDL-C) level to be reached. This consideration makes the ezetimibe/statin combination the ideal LDL-lowering agent to be combined with ubiquinol in CHF patients. However, particular caution is advisable with the use of strategies of extreme lowering of cholesterol that may negatively impact on myocardial function. All in all there is a strong case for considering co-administration of ubiquinol with statin therapy in patients with depressed or borderline myocardial function.
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Coenzyme Q10 (CoQ10) is a natural compound, is involved in the mitochondrial electron transfer chain (ETC) and plays an important pattern in adenosine triphosphate (ATP) production. Amelioration of ATP is related to abnormalities in cognitive function and psychiatric diseases. Previous studies have shown that depression is accompanied by the induction of inflammatory and oxidative stress pathways and amelioration of antioxidant status. In a recent study, we investigated the beneficial effects of CoQ10 on behavioral dysfunction and CoQ10 level in the rat brain. Therefore, intracerebroventricular (ICV) infusion of a single dose of streptozotocin (STZ, 0.2 mg/mouse) was used in adult male mice to induce depression. The behavioral data revealed a significant difference between the depression and control groups regarding the forced swim test (FST) and splash test results at 24 h following STZ treatment. Also, the validated and accurate high-performance liquid chromatography (HPLC) technique showed decreased CoQ10 level in the brain samples of the STZ group, compared to the controls. Our findings revealed that behavioral abnormalities due to STZ target mitochondria and affect energy metabolism and hemostasis, resulting in the initiation of oxidative damage in the brain. Besides, 4-week administration of CoQ10 could reverse the depressive like behavior and bioenergetic effects of STZ in the treated groups.
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We assessed whether dietary supplementation with coenzyme Q(10) improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q(10) or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F(2)-isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q(10) and decreased by -0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q(10) treatment resulted in a threefold increase in plasma coenzyme Q(10) (p < 0.001) but did not alter plasma F(2)-isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. Coenzyme Q(10) supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F(2)-isoprostane concentrations.
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There is evidence that plasma coenzyme Q(10) (CoQ(10)) levels decrease in patients with advanced chronic heart failure (CHF). However, it is not known whether oral CoQ(10) supplementation may improve cardiocirculatory efficiency and endothelial function in patients with CHF. We studied 23 patients in NYHA class II and III (20 men, three women, mean age 59+/-9 years) with stable CHF secondary to ischaemic heart disease [ejection fraction 37+/-7%], using a double-blind, placebo-controlled cross-over design. Patients were assigned to each of the following treatments: oral CoQ(10) (100 mg tid), CoQ(10) plus supervised exercise training (ET) (60% of peak VO(2), five times a week), placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak VO(2) and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ(10) and after ET as compared with placebo. CoQ(10) main effect was: peak VO(2)+9%, EDDBA +38%, systolic wall thickening score index (SWTI) -12%; ET produced comparable effects. CoQ(10) supplementation resulted in a four-fold increase in plasma CoQ(10) level, whereas the combination with ET further increased it. No side effects were reported with CoQ(10). Oral CoQ(10) improves functional capacity, endothelial function, and LV contractility in CHF without any side effects. The combination of CoQ(10) and ET resulted in higher plasma CoQ(10) levels and more pronounced effects on all the abovementioned parameters. However, significant synergistic effect of CoQ(10) with ET was observed only for peak SWTI suggesting that ET amplifies the already described effect of CoQ(10) on contractility of dysfunctional myocardium.
Article
Superoxide dismutase (SOD) activity was measured by seven assay methods. The nitrite method was found to be the best for our SOD assay kit. This method was then modified to give better sensitivity and minimize interference by coexisting protein, a factor which has been previously ignored. Hydroxylamine or its O-sulfonic acid, xanthine oxidase, hypoxanthine, EDTA, and the sample were incubated with or without KCN at pH 8.2, 37°C, for 30 min. Diazo dye-forming reagent was added and the absorption was measured at 550 nm. Human plasma and erythrocyte lysate from healthy adults and Down's syndrome patients were assayed by this SOD kit and by the cytochrome c method. Our kit gave 8.5 times higher sensitivity than the cytochrome c method. This high sensitivity allowed the use of a simple spectrophotometer and, moreover, only one dilution was needed to determine the SOD unit with the help of our formulas. Good recovery, reproducibility, and stability of reagents were demonstrated.
Article
Objectives: This study sought to investigate whether the identification of hibernating myocardium by low dose dobutamine stress echocardiography (LDSE) may predict an improvement in functional capacity after moderate exercise training in patients with ischemic cardiomyopathy. Another objective was to assess whether exercise training may affect the outcome. Background: There is evidence that exercise training improves left ventricular (LV) function as well as functional capacity in patients with a previous myocardial infarction and LV dysfunction. We hypothesized that the magnitude of these improvements might be related to the extent of hibernating myocardium. Methods: We studied 71 consecutive patients 56+/-9 years old (mean +/- SD) with chronic heart failure secondary to ischemic cardiomyopathy (LV ejection fraction [LVEF] <40%). All patients were in sinus rhythm and were clinically stable during the previous 3 months. Patients were randomized into two matched groups. Group T (n = 36) underwent exercise training at 60% of peak oxygen uptake (Vo2) three times a week for 10 weeks. Group C (n = 35) did not exercise. At study entry and end, all patients underwent an exercise test with gas exchange analysis and LDSE (5 to 20 microg/kg body weight per min). Results: At baseline, a positive contractile response (CS+) to LDSE was observed in 317 of 576 segments in group T and 291 of 560 segments in group C. After 10 weeks, peak Vo2 and peak work rate increased only in trained patients (peak Vo2: from 16.2+/-3 to 20.8+/-4 ml/kg per min; work capacity: from 108+/-20 to 131+/-25 W, p < 0.001 vs. group C for both). The presence of CS+ at baseline was associated with a sensitivity of 70% and a specificity of 77% for predicting an increase in the functional capacity after exercise training. Positive and negative predictive values of LDSE were 84% and 59%, respectively. Independent predictors of cardiac events were a pre-to-posttraining difference in LVEF at peak dobutamine infusion and the presence of a viable response at baseline (p = 0.004 and 0.008, respectively). The log-rank test demonstrated that trained patients had a significantly lower probability of cardiac events during follow-up than sedentary control patients (p < 0.001). Conclusions: The presence of hibernating myocardium as assessed by LDSE predicts the magnitude of improvement in functional capacity after moderate exercise training in patients with chronic heart failure. A significant increase in functional capacity after exercise training is associated with a lower incidence of cardiac events during follow-up.
Article
1Age-associated deterioration of arterial function may result from long-lasting oxidative stress. Since coenzyme Q (Q10) has been suggested to protect the vascular endothelium from free radical-induced damage, we investigated the effects of long-term dietary Q10 supplementation on arterial function in senescent Wistar rats.2At 16 months of age, 18 rats were divided into two groups. The control group was kept on a standard diet while the other group was supplemented with Q10 (10 mg kg−1 day−1). In addition, nine rats (age 2 months) also ingesting a standard diet were used as the young control group. After 8 study weeks the responses of the mesenteric arterial rings in vitro were examined.3Endothelium-independent arterial relaxations to isoprenaline and nitroprusside (SNP) were attenuated in aged rats. Increased dietary Q10 clearly enhanced the relaxation to isoprenaline, but did not affect the response to SNP. In addition, vasodilation of noradrenaline-precontracted rings to acetylcholine (ACh), which was also impaired in aged vessels, was improved after Q10 supplementation. Cyclooxygenase inhibition with diclofenac enhanced the relaxation to ACh only in young rats, while it abolished the difference between the old controls and Q10 supplemented rats, suggesting that the improved endothelium-dependent vasodilation observed in Q10 supplemented rats was largely mediated by prostacyclin (PGI2).4In conclusion, long-term Q10 supplementation improved endothelium-dependent vasodilation and enhanced β-adrenoceptor-mediated arterial relaxation in senescent Wistar rats. The mechanisms underlying the improvement of endothelial function may have included augmented endothelial production of PGI2, increased sensitivity of smooth muscle to PGI2, or both.British Journal of Pharmacology (1998) 124, 1500–1506; doi:10.1038/sj.bjp.0701970
Article
The clinical experience in cardiology with CoQ10 includes studies on congestive heart failure, ischemic heart disease, hypertensive heart disease, diastolic dysfunction of the left ventricle, and reperfusion injury as it relates to coronary artery bypass graft surgery. The CoQ10-lowering effect of HMG-CoA reductase inhibitors and the potential adverse consequences are of growing concern. Supplemental CoQ10 alters the natural history of cardiovascular illnesses and has the potential for prevention of cardiovascular disease through the inhibition of LDL cholesterol oxidation and by the maintenance of optimal cellular and mitochondrial function throughout the ravages of time and internal and external stresses. The attainment of higher blood levels of CoQ10 (>3.5 μg/ml) with the use of higher doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement. In this communication, 34 controlled trials and several open-label and long-term studies on the clinical effects of CoQ10 in cardiovascular diseases are reviewed.
Article
An electrochemical study was carried out on 1,4-benzoquinone, duroquinone, coenzymes Q 0 and Q 10 in the absence and in the presence of molecular oxygen in aprotic (DMF) and protic (DMF/H2O 95:5 (v/v)) media. Water was added because the investigated reactions are deeply influenced by the presence of protons. Q 0 and Q 10 exhibited a similar electrochemical behaviour. Since Q 0 is more soluble in protic medium than the biologically more important analogue Q 10 , it was chosen as a model for a more detailed investigation. Voltammetric studies of Q 0 carried out in aprotic and protic media in the presence of oxygen showed that, besides simple O2 ·− dismutation, the Q 0 promoted dismutation of O2 ·− should also be considered. Spectroelectrochemical experiments with the same experimental conditions support the electrochemical results, showing that in the presence of superoxide and in aprotic medium semiquinone Q 0 ·− gives rise to a disproportionation equilibrium, while in the presence of water it tends to be reoxidized to the starting Q 0 by OOH·. EPR measurements are also in agreement with these results.
Article
The saturation kinetics of NADH and succinate oxidation for Coenzyme Q (CoQ) has been re-investigated in pentane-extracted lyophilized beef heart mitochondria reconstituted with exogenous CoQ10. The apparent 'Km' for CoQ10 was one order of magnitude lower in succinate cytochrome c reductase than in NADH cytochrome c reductase. The Km value in NADH oxidation approaches the natural CoQ content of beef heart mitochondria, whereas that in succinate oxidation is close to the content of respiratory chain enzymes.
Article
The ability of different homologues of Coenzyme Q to quench O2- was tested in vitro with three experimental systems known to generate O2-. Two of them were biological generators, namely the xanthine-xanthine oxidase system and the cyanide-insensitive NADPH oxidase of polymorphonuclear leucocytes. The third was a chemical generator of O2-, the NADH-phenazine methosulphate-nitroblue tetrazolium mixture. Short-side-chain ubiquinones were found to be the most potent scavengers of O2-, being effective at concentrations as low as 10(-7) M. This finding might be ascribed to the relatively greater water-solubility of the lower homologues of CoQ. We postulate that CoQ10 may well exert such an O2- -scavenging mechanisms in vivo where it is inserted in its natural phospholipid environment.
Article
Extracellular superoxide dismutase (SOD) has previously been shown to be the major SOD isoenzyme in extracellular fluids. Upon chromatography on heparin-Sepharose it was separated into three fractions: A, without affinity; B, with intermediate affinity; and C, with relatively strong heparin affinity. Intravenous injection of heparin leads to a prompt increase in plasma extracellular-superoxide-dismutase (EC-SOD) activity. Heparin induces no release of EC-SOD from blood cells, nor does it activate EC-SOD in plasma, indicating that the source of the released enzyme is the endothelial-cell surfaces. No distinct saturation could be demonstrated in a dose-response curve up to 200 i.u. of heparin per kg body weight, showing that the releasing potency of heparin is lower for EC-SOD than for previously investigated heparin-released factors. Chromatography of human plasma on heparin-Sepharose shows nearly equal amounts of EC-SOD fractions A, B and C. Heparin induces specifically the release of fraction C. The findings point to the existence of an equilibrium of EC-SOD fraction C between the plasma phase and endothelial-cell surfaces. The major part of EC-SOD in the vasculature seems to be located on endothelial-cell surfaces.
Article
The activity of superoxide dismutase isoenzymes was determined in knee joint synovial fluid from 21 patients with rheumatoid arthritis, nine patients with reactive arthritides, and from 17 patients before arthroscopy or arthrotomy for suspected meniscal or ligament injury (controls). Extracellular superoxide dismutase was the major isoenzyme and accounted for about 80% of the total superoxide dismutase activity in the controls. The pattern of the superoxide dismutase isoenzymes was significantly different in rheumatoid arthritis, extracellular (EC) superoxide dismutase being half, CuZn superoxide dismutase double, and the total superoxide dismutase activity a third lower than the activity in the synovial fluid of the controls. The superoxide dismutase activities were similar in synovial fluid from the controls and from the patients with reactive arthritides. The total superoxide dismutase activity was almost three times higher in control synovial fluid than in normal human plasma, but 300 times lower than in human tissues.
Article
The contents of extracellular superoxide dismutase, CuZn superoxide dismutase and Mn superoxide dismutase were determined in tissues from nine mammalian species. The pattern of CuZn superoxide dismutase distribution was similar in all species, with high activity in metabolically active organs such as liver and kidney and low activity in, for example, skeletal muscle. Mn superoxide dismutase activity was high in organs with high respiration, such as liver, kidney, and myocardium. Overall the Mn superoxide dismutase activity in organs was almost as high as the CuZn superoxide dismutase activity. The content of extracellular superoxide dismutase was, almost without exception, lower than the content of the other isoenzymes. The pattern of tissue distribution was distinctly different from those of CuZn superoxide dismutase and Mn superoxide dismutase. The tissue distribution of extracellular superoxide dismutase differed among species, but in general there was much in lungs and kidneys and little in skeletal muscle. In man, pig, sheep, cow, rabbit and mouse the overall tissue extracellular superoxide dismutase activities were similar to each other, whereas dog, cat and rat tissues contained distinctly less. There was no general correlation between the tissue extracellular superoxide dismutase activity of any of the various species and the variable plasma activity. The ratio between the plasma and the overall tissue activities was high, for some species over unity, providing further evidence for the notion that one role of extracellular superoxide dismutase is as a plasma protein.
Article
Serum from healthy volunteers contained very little CuZn superoxide dismutase. Larger amounts were found in serum from patients with impaired renal function, and there was a good correlation between serum creatinine and serum CuZn superoxide dismutase content. Almost all superoxide dismutase activity of human serum was cyanide sensitive, and was found to be given by a factor(s) with a molecular mass of approximately 130000. The factor was found in all human extracellular fluids investigated: plasma, serum, lymph, ascites and cerebrospinal fluid. The factor was not recognized by radioimmunoassay for human CuZn superoxide dismutase, and it was not inhibited by rabbit antibodies against human CuZn superoxide dismutase. A similar high-molecular mass factor was found in plasma from all mammals investigated: horse, cow, pig, dog, cat, rabbit, rat and mouse. The activities differed much among species and were mostly higher than those found in human serum/plasma.
Article
Extracellular-superoxide dismutase [EC 1.15.1.1] (EC-SOD) is a secretory, tetrameric glycoprotein. A prominent feature of EC-SOD is its affinity for heparin. This enzyme in serum is heterogeneous with regard to heparin-affinity and can be divided into five fractions (I) to (V) by heparin-HPLC, whereas fibroblast-secreted EC-SOD consists mainly of form (V). An intravenous injection of 50 i.u. of heparin/kg body weight into two healthy volunteers led to an immediate rise of serum EC-SOD level by 2.4-2.8-fold. Only form (V), which was a minor component in pre-heparin serum, was increased by the intravenous injection. The half-life of serum EC-SOD after the prompt rise was about 90 min. The in vivo experiment using rats and an in vitro experiment strongly suggested the EC-SOD released into the plasma reconstituted the interaction with glycocalyx on the vascular endothelial cell surface in accordance with the elimination of heparin from the vascular system.
Article
This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN; an endothelium-independent dilator), using high-resolution external vascular ultrasound. At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/-6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise program. Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease.
Article
We used in vivo phosphorus magnetic resonance spectroscopy (31P-MRS) to study the effect of CoQ10 on the efficiency of brain and skeletal muscle mitochondrial respiration in ten patients with mitochondrial cytopathies. Before CoQ, brain [PCr] was remarkably lower in patients than in controls, while [Pi] and [ADP] were higher. Brain cytosolic free [Mg2+] and delta G of ATP hydrolysis were also abnormal in all patients. MRS also revealed abnormal mitochondrial function in the skeletal muscles of all patients, as shown by a decreased rate of PCr recovery from exercise. After six-months of treatment with CoQ (150 mg/day), all brain MRS-measurable variables as well as the rate of muscle mitochondrial respiration were remarkably improved in all patients. These in vivo findings show that treatment with CoQ in patients with mitochondrial cytopathies improves mitochondrial respiration in both brain and skeletal muscles, and are consistent with Lenaz's view that increased CoQ concentration in the mitochondrial membrane increases the efficiency of oxidative phosphorylation independently of enzyme deficit.
Article
Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospectively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates. Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine, sympathetic activation by cold pressor testing, dilator responses to increased blood flow, and dilation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral artery revascularization) served as outcome variables over a median follow-up period of 7.7 years. Patients suffering from cardiovascular events during follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion (P=0. 009) and cold pressor testing (P=0.002), as well as significantly blunted vasodilator responses to increased blood flow (P<0.001) and the intracoronary injection of nitroglycerin (P=0.001). Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis. By multivariate analysis, all tests of coronary vasoreactivity were significant, independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself. Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates. Thus, the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.
Article
Increased inactivation of nitric oxide by oxygen free radicals contributes to endothelial dysfunction in patients with coronary artery disease (CAD). We therefore determined the activity of extracellular superoxide dismutase (EC-SOD), the major antioxidant enzyme system of the vessel wall, and its relation to flow-dependent, endothelium-mediated dilation (FDD) in patients with CAD. SOD isoenzyme activity was determined in coronary arteries from 10 patients with CAD and 10 control subjects. In addition, endothelium-bound EC-SOD activity (eEC-SOD), released by heparin bolus injection, and FDD of the radial artery were measured in 35 patients with CAD and 15 control subjects. FDD, determined by high-resolution ultrasound, was assessed at baseline, after intra-arterial infusion of vitamin C, N-monomethyl-L-arginine, and combination of both. EC-SOD activity in coronary arteries (control subjects: 126+/-14; CAD: 63+/-11 U/mg protein; P<0.01) and eEC-SOD activity in vivo (control subjects: 14.5+/-1.1; CAD: 3.8+/-1.1 U. mL(-1). min(-1); P<0.01) were reduced in patients with CAD. Activity of eEC-SOD was positively correlated with FDD (r=0.47; P<0. 01) and negatively with the effect of the antioxidant vitamin C on FDD (r=-0.59; P<0.01). In young individuals with hypercholesterolemia, however, eEC-SOD activity was increased (21. 0+/-1.2 U. mL(-1). min(-1); n=10; P<0.05). In patients with CAD, vascular EC-SOD activity is substantially reduced. The close relation between endothelium-bound EC-SOD activity and FDD suggests that reduced EC-SOD activity contributes to endothelial dysfunction in patients with CAD. In young hypercholesterolemic individuals, however, endothelium-bound EC-SOD activity is increased and may, in part, counteract impairment of endothelial function as the result of increased formation of oxygen free radicals.
Article
Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology.
Article
Excessive production and/or inadequate removal of reactive oxygen species, especially superoxide anion (O(2)(*-)), have been implicated in the pathogenesis of many cardiovascular diseases, including atherosclerosis, hypertension, diabetes, and in endothelial dysfunction by decreasing nitric oxide (NO) bioactivity. Since the vascular levels of O(2)(*-) are regulated by the superoxide dismutase (SOD) enzymes, a role of SOD in the cardiovascular disease is of substantial interest. Particularly, a major form of SOD in the vessel wall is the extracellular SOD (ecSOD). This review will discuss the characteristics of ecSOD and the role of ecSOD in cardiovascular diseases.
Article
Energy starvation of the myocardium is probably a dominant feature of heart failure and attention has been directed towards agents which may stabilize myocardial metabolism and maintain adequate energy stores. A reduced myocardial tissue content of the essential redox-component and natural antioxidant Coenzyme Q10 (CoQ10) has been detected in patients with heart failure and the observed level of CoQ10 deficiency was correlated to the severity of heart failure. CoQ10 fulfills various criteria of an obvious adjunct in patients with symptomatic heart failure: it is devoid of significant side effects and it improves symptoms and quality of life. Till this date, several double-blind placebo-controlled trials with CoQ10 supplementation in more than 1000 patients have been positive and statistically significant with respect to various clinical parameters, e.g. improvement in NYHA Class, exercise capacity and reduced hospitalisation frequency. Also treatment with CoQ10 led to a significant improvement of relevant hemodynamic parameters. In only 3 out of 13 double-blind studies comprising 10% of the total number of patients treated the results were neutral. Thus, based on the available controlled data CoQ10 is a promising, effective and safe approach in chronic heart failure. This is why a double-blind multicenter trial with focus on morbidity and mortality has been planned to start in 2003: Q-SYMBIO. Patients in NYHA classes III to IV (N=550) receiving standard therapy are being randomized to treatment with CoQ10 100 mg t.i.d. or placebo in parallel groups. End-points in a short-term evaluation phase of 3 months include symptoms, functional capacity and biomarker status (BNP). The aim of a subsequent 2-year follow-up study is to test the hypothesis that CoQ10 may reduce cardiovascular morbidity (unplanned cardiovascular hospitalisation due to worsening heart failure) and mortality as a composite endpoint. This trial should help to establish the future role of CoQ10 as part of a maintenance therapy in patients with chronic heart failure.
Article
Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phosphorylation disorders, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q(10) (ubiquinone), other antioxidants such as ascorbic acid and vitamin E, riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of these therapies is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. In the present study, we demonstrate for the first time that there is a significant increase in ATP synthetic capacity in lymphocytes from patients undergoing cofactor treatment. We also examined in vitro cofactor supplementation in control lymphocytes in order to determine the effect of the individual components of the cofactor treatment on ATP synthesis. A dose-dependent increase in ATP synthesis with CoQ(10) incubation was demonstrated, which supports the proposal that CoQ(10) may have a beneficial effect in the treatment of oxidative phosphorylation (OXPHOS) disorders.
Article
Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an agent for estimating coronary endothelial function. In contrast to ACh, there is no evidence for a relationship between FMD and coronary vasodilation to bradykinin (BK). The aim of this study was to compare the flow-mediated vasodilation of brachial artery with coronary vasomotor responses to intracoronary ACh or BK in patients with an angiographically normal left anterior descending coronary artery. Ninety-one patients underwent the cardiac catheterization examination with coronary endothelial function testing and the brachial ultrasound study. BK (0.2, 0.6, 2.0 microg/min) and ACh (3, 10, 30 microg/min) were administered into the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by the Doppler flow velocity measurement. Coronary diameters were measured by the quantitative coronary angiography. The assessment of endothelial function in the brachial artery was made in response to reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose-dependent increases in epicardial coronary diameter and blood flow. There was a significant positive correlation between FMD- and BK-induced vasodilations of epicardial coronary arteries (0.2 microg/min: r = 0.30; 0.6 microg/min: r = 0.42; 2.0 microg/min: r = 0.44, P < 0.01, respectively) and resistance coronary arteries (0.2 microg/min: r = 0.40; 0.6 microg/min: r = 0.56; 2.0 microg/min: r = 0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of resistance but not epicardial coronary arteries. No correlation was seen between nitroglycerin-induced brachial artery vasodilation and BK-induced coronary vasodilation. The endothelial dysfunction of peripheral arteries correlated well with that of the coronary arteries especially vasomotor responses to BK.
Article
Objectives: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. Methods: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. Results: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. Conclusions: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.
Article
There is growing evidence that the altered production and/or spatiotemporal distribution of reactive oxygen and nitrogen species creates oxidative and/or nitrosative stresses in the failing heart and vascular tree, which contribute to the abnormal cardiac and vascular phenotypes that characterize the failing cardiovascular system. These derangements at the integrated system level can be interpreted at the cellular and molecular levels in terms of adverse effects on signaling elements in the heart, vasculature, and blood that subserve cardiac and vascular homeostasis.
Article
Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects. However, the molecular mechanisms to explain pleiotrophic effects of CoQ10 are not clear yet and it is likely that CoQ10 targets the expression of multiple genes. We therefore utilized gene expression profiling based on human oligonucleotide sequences to examine the expression in the human intestinal cell line CaCo-2 in relation to CoQ10 treatment. CoQ10 caused an increased expression of 694 genes at threshold-factor of 2.0 or more. Only one gene was down-regulated 1.5-2-fold. Real-time RT-PCR confirmed the differential expression for seven selected target genes. The identified genes encode proteins involved in cell signalling (n = 79), intermediary metabolism (n = 58), transport (n = 47), transcription control (n = 32), disease mutation (n = 24), phosphorylation (n = 19), embryonal development (n = 13) and binding (n = 9). In conclusion, these findings indicate a prominent role of CoQ10 as a potent gene regulator. The presently identified comprehensive list of genes regulated by CoQ10 may be used for further studies to identify the molecular mechanism of CoQ10 on gene expression.
Article
Accumulated evidence has shown that reactive oxygen species (ROS) are important mediators of cell signaling events such as inflammatory reactions (superoxide) and the maintenance of vascular tone (nitric oxide). However, overproduction of ROS such as superoxide has been associated with the pathogenesis of a variety of diseases including cardiovascular diseases, neurological disorders, and pulmonary diseases. Antioxidant enzymes are, in part, responsible for maintaining low levels of these oxygen metabolites in tissues and may play key roles in controlling or preventing these conditions. One key antioxidant enzyme implicated in the regulation of ROS-mediated tissue damage is extracellular superoxide dismutase (EC-SOD). EC-SOD is found in the extracellular matrix of tissues and is ideally situated to prevent cell and tissue damage initiated by extracellularly produced ROS. In addition, EC-SOD is likely to play an important role in mediating nitric oxide-induced signaling events, since the reaction of superoxide and nitric oxide can interfere with nitric oxide signaling. This review will discuss the regulation of EC-SOD and its role in a variety of oxidant-mediated diseases.
Superoxide sidmutase in extracellular fluids Table 2 Cardiopulmonary exercise testing results CoQ 10 Placebo Baseline 1 Month Baseline 1 Month Peak VO 2 (mL/kg/min)
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Marklund SL, Hellner L. Superoxide sidmutase in extracellular fluids. Clin Chim Acta 1982;126:41–51. Table 2 Cardiopulmonary exercise testing results CoQ 10 Placebo Baseline 1 Month Baseline 1 Month Peak VO 2 (mL/kg/min)
Exercise training enhances endothelial function in young men Estornell E, Fato R, Castelluccio C et al. Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart mitochondria
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Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE. Exercise training enhances endothelial function in young men. J Am Coll Cardiol 1999;33:1379–1385. 18. Estornell E, Fato R, Castelluccio C et al. Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart mitochondria. FEBS Lett 1992;311:107–109.
Effect of CoQ 10 administration on VO 2 max and diastolic function in athletes
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Amadio A, Palermo R, Peloni G, Littarru GP. Effect of CoQ 10 administration on VO 2 max and diastolic function in athletes. In: Folkers K, Littarru GP, Yamagami T, eds. Biomedical and Clinical Aspects of Coenzyme Q. Vol. VI. Elsevier North Holland; 1991.
Cofactor treatment improves ATP synthetic capacity in patients with oxidative phosphorylation disorders
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