Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10.
Ontology highlight
ABSTRACT:
SUBMITTER: Biglan KM
PROVIDER: S-EPMC4115297 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10.
Biglan K M KM Dorsey E R ER Evans R V V RV Ross C A CA Hersch S S Shoulson I I Matson W W Kieburtz K K
Journal of Huntington's disease 20120101 1
We analyzed plasma 8OHdG concentrations in 20 individuals enrolled in the Pre-2CARE study before and after treatment with CoQ. Treatment resulted in a mean reduction in 8OHdG of 2.9 ± 2.9 pg/ml for the cohort (p = 0.0003) and 3.0 ± 2.6 pg/ml, for the HD group (p = 0.002). Baseline 8OHdG levels were not different between individuals with HD and controls (19.3 ± 3.2 pg/ml vs. 19.5 ± 4.7 pg/ml, p = 0.87) though baseline CoQ levels were elevated in HD compared with controls (p < 0.001). CoQ treatmen ...[more]
Similar Datasets
Project description:ObjectiveTo test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD.MethodsWe performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach.ResultsAn interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study.ConclusionsThese data do not justify use of CoQ as a treatment to slow functional decline in HD.Clinicaltrialsgov identifierNCT00608881.Classification of evidenceThis article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.
| S-EPMC5224719 | biostudies-literature
Project description:PurposeTo investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk.Materials and methodsA retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing.ResultsThe mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11-14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518-0.751).ConclusionThe study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.
| S-EPMC6636459 | biostudies-literature
Project description:In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.
| S-EPMC4913434 | biostudies-literature
Project description:Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme Q10 (CoQ10) with statins. The goal of the current research is to assess the efficacy of combined treatment of CoQ10 with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of CoQ10 (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin onlytreatment, CoQ10 supplementation significantlyreduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, CoQ10 supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and CoQ10 were increased in the CoQ10 co-treated group. These results indicate that CoQ10 treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary CoQ10 is helpful for solving problem of obese metabolism, so the multiple prescription of CoQ10 makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism.
| S-EPMC4774498 | biostudies-literature
Project description:Identifying diseases displaying chronic low plasma Coenzyme Q10 (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016. Patients were classified into 6 different groups: control group of healthy participants, phenylketonuric patients (PKU), patients with mucopolysaccharidoses (MPS), patients with other inborn errors of metabolism (IEM), patients with neurogenetic diseases, and individuals with neurological diseases with no genetic diagnosis. Plasma total CoQ was measured by reverse-phase high-performance liquid chromatography with electrochemical detection and ultraviolet detection at 275 nm. ANOVA with Bonferroni correction showed that plasma CoQ values were significantly lower in the PKU and MPS groups than in controls and neurological patients. The IEM group showed intermediate values that were not significantly different from those of the controls. In PKU patients, the Chi-Square test showed a significant association between having low plasma CoQ values and being classic PKU patients. The percentage of neurogenetic and other neurological patients with low CoQ values was low (below 8%). In conclusión, plasma CoQ monitoring in selected groups of patients with different IEM (especially in PKU and MPS patients, but also in IEM under protein-restricted diets) seems advisable to prevent the possibility of a chronic blood CoQ suboptimal status in such groups of patients.
| S-EPMC6349877 | biostudies-literature
Project description:For a number of years, coenzyme Q10 (CoQ10) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in blood plasma, and extensively investigated its antioxidant role. These 2 functions constitute the basis for supporting the clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is recognized as an obligatory cofactor for the function of uncoupling proteins and a modulator of the mitochondrial transition pore. Furthermore, recent data indicate that CoQ10 affects the expression of genes involved in human cell signaling, metabolism and transport, and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant strategy in many diseases that may provide a significant symptomatic benefit.
| S-EPMC4112525 | biostudies-literature
Project description:Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65-74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product-IP); ubiquinol capsules (the comparative product-CP); and ubiquinone capsules (the standard product-SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3-4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9-3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.
| S-EPMC7146408 | biostudies-literature
Project description:ObjectiveThe vascular benefits of statins might be attenuated by inhibition of coenzyme Q(10) (CoQ(10)) synthesis. We investigated whether oral CoQ(10) supplementation improves endothelial dysfunction in statin-treated type 2 diabetic patients.Research design and methodsIn a double-blind crossover study, 23 statin-treated type 2 diabetic patients with LDL cholesterol <2.5 mmol/l and endothelial dysfunction (brachial artery flow-mediated dilatation [FMD] <5.5%) were randomized to oral CoQ(10) (200 mg/day) or placebo for 12 weeks. We measured brachial artery FMD and nitrate-mediated dilatation (NMD) by ultrasonography. Plasma F(2)-isoprostane and 24-h urinary 20-hydroxyeicosatetraenoic acid (HETE) levels were measured as systemic oxidative stress markers.ResultsCompared with placebo, CoQ(10) supplementation increased brachial artery FMD by 1.0 +/- 0.5% (P = 0.04), but did not alter NMD (P = 0.66). CoQ(10) supplementation also did not alter plasma F(2)-isoprostane (P = 0.58) or urinary 20-HETE levels (P = 0.28).ConclusionsCoQ(10) supplementation improved endothelial dysfunction in statin-treated type 2 diabetic patients, possibly by altering local vascular oxidative stress.
| S-EPMC2671099 | biostudies-literature
Project description:Ubiquinone (coenzyme Q(10) or CoQ(10)) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. Deficiency of CoQ(10) (MIM 607426) has been associated with five different clinical presentations that suggest genetic heterogeneity, which may be related to the multiple steps in CoQ(10) biosynthesis. Patients with all forms of CoQ(10) deficiency have shown clinical improvements after initiating oral CoQ(10) supplementation. Thus, early diagnosis is of critical importance in the management of these patients. This year, the first molecular defect causing the infantile form of primary human CoQ(10) deficiency has been reported. The availability of genetic testing will allow for a better understanding of the pathogenesis of this disease and early initiation of therapy (even presymptomatically in siblings of patients) in this otherwise life-threatening infantile encephalomyopathy.
| S-EPMC1832150 | biostudies-literature
Project description:Coenzyme Q10 (CoQ10) is a key component of the mitochondrial electron transfer chain and is one of the most important cellular antioxidants. We previously reported that glycoprotein saposin B (SapB) binds CoQ10 in human cells. To elucidate the physiological role of SapB and its precursor, prosaposin (Psap), we prepared stable transfectants of HepG2 that overexpress wild-type human Psap (Wt-Tf). We also established a SapB domain mutated Psap (Mt-Tf) in which cysteine(198) was replaced with serine to disrupt three dimensional protein structure by the loss of S-S bridging. Psap knockdown (KD) strains were also examined. Western blotting analysis confirmed overexpression or knockdown of Psap in these HepG2 cells. The cellular ratios of CoQ10 to free cholesterol (FC) significantly decreased in the order of Wt-Tf>parental>Mt-Tf>KD. Additionally, the ratios of CoQ10/FC in mitochondrial fractions decreased in the order of Wt-Tf>parental>KD. These data indicate that Psap and/or SapB regulate CoQ10 levels in HepG2 cells, especially in their mitochondria.
| S-EPMC4186375 | biostudies-literature