Concept: Coenzyme Q10
Chronic Fatigue Syndrome (CFS) is a complex condition, characterized by severe disabling fatigue with no known cause, no established diagnostic tests, and no universally effective treatment. Several studies have proposed symptomatic treatment with coenzyme Q10 (CoQ10) and nicotinamide adenine dinucleotide (NADH) supplementation. The primary endpoint was to assess the effect of CoQ10 plus NADH supplementation on age-predicted maximum heart rate (max HR) during a cycle ergometer test. Secondary measures included fatigue, pain and sleep.
Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.
Low seminal plasma concentrations of coenzyme Q10 (CoQ10) have been correlated with impaired sperm parameters, but the exact mechanism remains of dominating interest. This randomised, placebo-controlled study examined the effect of CoQ10 on catalase, superoxide dismutase (SOD) and F(2) -isoprostanes in seminal plasma in infertile men and their relation with CoQ10 concentration. Sixty infertile men with idiopathic oligoasthenoteratozoospermia (OAT) were randomised to receive 200 mg d(-1) of CoQ10 or placebo for 3 months. 47 persons of them completed the study. Semen analysis, anthropometric measurements, diet and physical activity assessment were performed for subjects before and after treatment. Independent and paired t-test, chi-square test and ancova were compared outcomes of supplementation between two groups. CoQ10 levels increased from 44.74 ± 36.47 to 68.17 ± 42.41 ng ml(-1) following supplementation in CoQ10 (P < 0.001). CoQ10 group had higher catalase and SOD activity than the placebo group. There was a significant positive correlation between CoQ10 concentration and normal sperm morphology (P = 0.037), catalase (P = 0.041) and SOD (P < 0.001). Significant difference was shown between the mean of changes in seminal plasma 8-isoprostane in two groups (P = 0.003) after supplementation. Three-month supplementation with CoQ10 in OAT infertile men can attenuate oxidative stress in seminal plasma and improve semen parameters and antioxidant enzymes activity.
PURPOSE: To investigate the protective effects of Coenzyme Q10 (CoQ10) on bladder dysfunction in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). MATERIALS AND METHODS: Twenty-four 16-week-old male Sprague-Dawley rats were divided into four groups (six rats in each group; group 1, untreated sham-operated rats; group 2, CoQ10-treated sham-operated rats; group 3, untreated CBI rats; group 4, CoQ10-treated CBI rats). Groups 3 and 4 received an endothelial injury of the iliac arteries and were fed a 2% cholesterol diet for eight weeks. Groups 2 and 4 were treated with CoQ10, and the others were treated with vehicle for 4 weeks. Eight weeks after the operations, we performed continuous in vivo cystometry, in vitro detrusor muscle strip study, and malondialdehyde (MDA) assay. Histological examinations of the bladder walls and iliac arteries were also performed. RESULTS: Results from in vivo cystometry revealed that the administration of CoQ10 after induction of CBI prolonged the micturition frequency and intercontraction interval and increased bladder capacity in comparison to untreated CBI rats. In the detrusor muscle strip study, the administration of CoQ10 after induction of CBI increased the contractile responses compared to untreated CBI rats. CBI rats also showed higher MDA levels in bladder tissues and serum than the other groups. CBI induced submucosal fibrosis of the bladder walls and a degenerative change in the media of the blood vessels, as shown on histologic examinations. CONCLUSIONS: Our study suggests that CoQ10 acts as an antioxidant to protect bladder function in chronic bladder ischemia model.
Objective: The objective of this work was to prepare coenzyme Q10 loaded nanostructured lipid carriers (Q10-NLC) and evaluate its epidermal targeting effect. Methods: Q10-NLC was prepared by high-pressure microfluidics technique. Formulations and preparation parameters were optimized with response surface design. Q10-NLC was characterized by PCS, TEM, DSC and PXRD. The penetration of Q10 from the Q10-NLC formulations through skins and into skins were evaluated in vitro using Franz diffusion cells fitted with SD rat skins. In vitro release, long-term stability and light stability were also evaluated. Results: The results showed that the concentration of solid lipid and emulsifier in formulation had a significant influence on particle size. The optimized preparation parameters were magnetic stirring for 20 min, high stirring at 8000 rpm for 1 min and high-pressure microfluidics at 1200 bar for three cycles. The size of Q10-NLC prepared by optimized formulation and parameters was (151.7 ± 2.31) nm, polydispersity (PDI) 0.144, ζ potential was (-44.1 ± 1.68) mV, drug loading 2.51%, encapsulation efficiency 100%. In vitro release study, Q10-NLC showed fast release during the first 3 hours and prolonged release afterwards. In vitro skin permeation study, the accumulative uptake of Q10 in epidermal of Q10-NLC was 10.11 times over Q10 emulsion. After exposure to day light for 24 hours, the amount of Q10 in Q10-NLC decreased only 5.59%, while in Q10 emulsion decreased 24.61% and Q10-ethanol solution 49.74%. Conclusion: Q10-NLC exhibited a significant epidermal targeting effect, which was proved to be a promising carrier for topical delivery of Q10.
Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of east mitochondria. We classified > 3,300 proteins of mitochondria and mitochondria-associated fractions and defined 901 high-confidence mitochondrial proteins, expanding the set of mitochondrial proteins by 82. Our analysis includes protein abundance under fermentable and nonfermentable growth, submitochondrial localization, single-protein experiments, and subcellular classification of mitochondria-associated fractions. We identified mitochondrial interactors of respiratory chain supercomplexes, ATP synthase, AAA proteases, the mitochondrial contact site and cristae organizing system (MICOS), and the coenzyme Q biosynthesis cluster, as well as mitochondrial proteins with dual cellular localization. The integrative proteome provides a high-confidence source for the characterization of physiological and pathophysiological functions of mitochondria and their integration into the cellular environment.
Association between amyloid-β (Aβ) toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage has been demonstrated in the pathophysiology of Alzheimer’s disease (AD). In the early stages of the disease, the defect in energy metabolism was found to be severe. This may probably due to the Aβ and ROS-induced declined activity of complexes in electron transport chain (ETC) as well as damages to mitochondrial DNA. Though clinically inconclusive, supplementation with antioxidants are reported to be beneficial especially in the early stages of the disease. A mild to moderate improvement in dementia is possible with therapy using antioxidants viz coenzyme Q10 (ubiquinone), α-lipoic acid, selenium, omega-3 fatty acids and vitamin E, emphasize their possible role as adjuvant with the existing conventional treatment. Since mitochondrial dysfunction has been observed, a new therapeutic strategy called ‘Mitochondrial Medicine’ which is aimed to maintain the energy production as well as to ameliorate the enhanced apoptosis of nerve cells has been developed. Mitochondrial CoQ10, Szeto-Schiller peptide-31 and superoxide dismutase/catalase mimetic, EUK-207 were the mitochondrial targeted agents demonstrated in experimental studies. This article discusses the mitochondrial impairment and the possible mitochondria targeted therapeutic intervention in AD.
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder related to inflammation. Coenzyme Q10 (CoQ10) is a natural compound that has recently been considered as an anti-inflammatory factor. In the current study we aimed to evaluate the effects of CoQ10 supplementation on liver enzymes, inflammation status, and adipokines in patients with NAFLD.
To evaluate protective effect of coenzyme Q10 (CoQ10) in lacrimal glands against high-dose radioactive iodine (RAI)-associated oxidative damage.
Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function.