Coenzyme Q10 Redox Status Research Articles

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes

ObjectiveThe purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. MethodThis case–control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity‐matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. ResultsChildren with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low‐density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high‐density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=−0.31; p=0.022) and the duration of type 1 diabetes (r=−0.35, p=0.012). ConclusionPatients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes

ObjectiveThe purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. MethodThis case–control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. ResultsChildren with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=−0.31; p=0.022) and the duration of type 1 diabetes (r=−0.35, p=0.012). ConclusionPatients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts.

Aging is associated with sarcopenia, which is a loss of skeletal muscle mass and function. Coenzyme Q10 (CoQ10) is involved in several important functions that are related to bioenergetics and protection against oxidative damage; however, the role of CoQ10 as a determinant of muscular strength is not well documented. The aim of the present study was to evaluate the determinants of muscular strength by examining hand grip force in relation to CoQ10 status, gender, age and body mass index (BMI) in two independent cohorts (n = 334, n = 967). Furthermore, peak flow as a function of respiratory muscle force was assessed. Spearman’s correlation revealed a significant positive association between CoQ10/cholesterol level and hand grip in the basic study population (p<0.01) as well as in the validation population (p<0.001). In the latter, we also found a negative correlation with the CoQ10 redox state (p<0.01), which represents a lower percentage of the reduced form of CoQ10 (ubiquinol) in subjects who exhibit a lower muscular strength. Furthermore, the age of the subjects showed a negative correlation with hand grip (p<0.001), whereas BMI was positively correlated with hand grip (p<0.01), although only in the normal weight subgroup (BMI <25 kg/m2). Analysis of the covariance (ANCOVA) with hand grip as the dependent variable revealed CoQ10/cholesterol as a determinant of muscular strength and gender as the strongest effector of hand grip. In conclusion, our data suggest that both a low CoQ10/cholesterol level and a low percentage of the reduced form of CoQ10 could be an indicator of an increased risk of sarcopenia in humans due to their negative associations to upper body muscle strength, peak flow and muscle mass.

Omental adipocyte hypertrophy relates to coenzyme Q10 redox state and lipid peroxidation in obese women

Occurrence of oxidative stress in white adipose tissues contributes to its dysfunction and the development of obesity-related metabolic complications. Coenzyme Q10 (CoQ10) is the single lipophilic antioxidant synthesized in humans and is essential for electron transport during mitochondrial respiration. To understand the role of CoQ10 in adipose tissue physiology and dysfunction, the abundance of the oxidized and reduced (CoQ10red) isoforms of the CoQ10 were quantified in subcutaneous and omental adipose tissues of women covering the full range of BMI (from 21.5 to 53.2 kg/m(2)). Lean women displayed regional variations of CoQ10 redox state between the omental and subcutaneous depot, despite similar total content. Obese women had reduced CoQ10red concentrations in the omental depot, leading to increased CoQ10 redox state and higher levels of lipid hydroperoxide. Women with low omental CoQ10 content had greater visceral and subcutaneous adiposity, increased omental adipocyte diameter, and higher circulating interleukin-6 and C-reactive protein levels and were more insulin resistant. The associations between abdominal obesity-related cardiometabolic risk factors and CoQ10 content in the omental depot were abolished after adjustment for omental adipocyte diameter. This study shows that hypertrophic remodeling of visceral fat closely relates to depletion of CoQ10, lipid peroxidation, and inflammation.

Abstract 2455: Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines

Abstract Although it is well recognized that Coenzyme Q10 (CoQ10) is present in all cellular membrane structures, its effects on cellular functions other than mitochondrial regulation is poorly understood. The present study was aimed at gleaning insights into effect on CoQ10 on sub-cellular metabolism, regulation of the redox status, as well as gene regulation. A series of fluorescent probes were developed with the ability to report on the consequence of specific biological events in which CoQ10 was involved. The probes constituted fluorescently labeled CoQ10 analogues designed to track the distribution, biochemical and redox behaviour of CoQ10 in a non-invasive manner providing real time information in live cells. Compartmentalization of fluorescent labeled CoQ10 probe incorporated within BPM 31510 liposomal formulation was characterized in human derived primary non-disease and cancer cell lines. Cellular distribution of the fluorescent CoQ10 varied depending upon cell type. The fluorescent CoQ10 probes were designed and utility to provide a time resolved assessment on the redox state of CoQ10 in whole cells and organelles as a measure of the cell's overall and intracellular location specific metabolic micro-environments. The ratio of reduced and oxidized form of fluorescent CoQ10 was also examined in relation to ROS production in cancer cells. The overall results describes the presence of a constant redox flux influencing the redox state of CoQ10 within cancer and normal cells with significant variation depending on cell type and disease status. Citation Format: Katerina Krumova, Sumit Garg, Sirisha Dhavala, Vivek K. Vishnudas, Michael A. Kiebish, Rangaprasad Sarangarajan, Niven R. Narain. Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2455. doi:10.1158/1538-7445.AM2015-2455

Oxidized proportion of muscle coenzyme Q10 increases with age in healthy children.

Coenzyme Q10 (CoQ10) is synthesized in most human tissues, with high concentration in the skeletal muscle. CoQ10 functions in the mitochondrial respiratory chain and serves as a potent liphophilic antioxidant in membranes. CoQ10 deficiency impairs mitochondrial ATP synthesis and increases oxidative stress. It has been suggested that plasma CoQ10 status is not a robust proxy for the diagnosis of CoQ10 deficiency. We determined the concentration and redox-status of CoQ10 in plasma and muscle tissue from 140 healthy children (0.8-15.3 y) by high-performance liquid chromatography (HPLC) with electrochemical detection. There was no correlation between CoQ10 concentration or redox status between plasma and muscle tissue. Lipid-related CoQ10 plasma concentrations showed a negative correlation with age (Spearman's, P ≤ 0.02), but there was no significant age-related correlation for muscle concentration. In muscle tissue, we found a distinct shift in the redox status in favor of the oxidized proportion with increasing age (Spearman's, P ≤ 0.00001). Reference values for muscle CoQ10 concentration (40.5 ± 12.2 pmol/mg wet tissue) and CoQ10 redox status (46.8 ± 6.8% oxidized within total) were established for healthy children. The age-related redox shift in muscle tissue suggests changes in antioxidative defense during childhood. The reference values established here provide a necessary prerequisite for diagnosing early CoQ10 deficiency.

Hypersensitive response-like lesions 1 codes for AtPPT1 and regulates accumulation of ROS and defense against bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana.

Plants employ both basal and resistance gene (R gene)-mediated defenses in response to pathogens. Reactive oxygen species (ROS) are widely reported to play a central role in both basal and R gene-mediated defense; however, the nature of ROS has been less well established for basal defense. In addition, spatial distribution of redox moieties and mechanisms of plant responses during basal defense are poorly understood. We investigated redox signaling in Arabidopsis thaliana in response to virulent bacterial pathogen, focusing on the role of the mitochondria in balancing energy demands against generation of physiologically relevant ROS. Positional cloning of an Arabidopsis lesion mimic mutant identified a polyprenyl transferase involved in the biosynthesis of Coenzyme Q10 (CoQ), which leads to novel insights into physiological ROS levels and their role in basal resistance. Gain- and loss-of-function studies identified Coenzyme Q10 redox state to be a key determinant of ROS levels. These Coenzyme Q10 redox state-mediated ROS levels had a direct bearing on both response against pathogen and ability to thrive in high oxidative stress environments. We demonstrate that Coenzyme Q10 redox state generates an ROS threshold for a successful basal resistance response. Perturbation of the Coenzyme Q10 redox state has the potential to disrupt plant defense responses against bacterial pathogens. Coenzyme Q10 redox state is a key regulator of Arabidopsis basal resistance against bacterial pathogens.

Association between serum level of ubiquinol and NT-proBNP, a marker for chronic heart failure, in healthy elderly subjects.

Ubiquinone and ubiquinol represent the oxidized and reduced forms of Coenzyme Q10 (CoQ10). CoQ10 is present in membranes of almost all human tissues and organs, with highest concentration in the heart. In patients with heart failure, serum levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) are an indicator of disease severity. Here, we investigated the relationship between serum levels of CoQ10 and NT-proBNP in healthy volunteers of an elderly study population (mean age 52 years, n = 871). We found a negative association between serum levels of ubiquinol and NT-proBNP (P < 0.001). Accordingly, the CoQ10 redox state (% oxidized form of CoQ10) is positively associated with serum NT-proBNP level (P < 0.001). Compared to patients who survived a myocardial infarction (n = 21), healthy subjects have lower NT-proBNP level (500.39 ± 631.28 pg/ml vs. 76.90 ± 120.27 pg/ml, P < 0.001), higher ubiquinol serum level (0.43 ± 0.19 µmol/L vs. 0.71 ± 0.32 µmol/L; P < 0.001), and a lower CoQ10 redox state (27.6 ± 13.8% vs. 17.6 ± 10.1%; P < 0.001). Interestingly, ubiquinol supplementation (150 mg/day; 14 day; n = 53) slightly reduces the expression of CLCN6, a gene related to NT-proBNP level. In summary, higher serum levels of ubiquinol are associated with lower serum NT-proBNP levels in healthy elderly subjects. However, to what extent a high serum level of ubiquinol is a protective factor for heart failure remains to be elucidated in prospective studies.

Rapid assessment of the coenzyme Q10 redox state using ultrahigh performance liquid chromatography tandem mass spectrometry.

An improved method for accurate and rapid assessment of the coenzyme Q10 (CoQ10) redox state using ultrahigh performance liquid chromatography tandem mass spectrometry was described, with particular attention given to the instability of the reduced form of CoQ10 during sample preparation, chromatographic separation and mass spectrometric detection. As highly lipophilic compounds in complex biological matrices, both reduced and oxidized forms of CoQ10 were extracted simultaneously from the tissue samples by methanol which is superior to ethanol and isopropanol. After centrifugation, the supernatants were immediately separated on a C18 column with isocratic elution using methanol containing 2 mM ammonium acetate as a non-aqueous mobile phase, and detected by positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring (MRM) mode. Ammonium acetate as an additive in methanol provided enhanced mass spectrometric responses for both forms of CoQ10, primarily due to stable formation of adduct ions [M + NH4](+), which served as precursor ions in positive ionization MRM transitions. The assay showed a linear range of 8.6-8585 ng mL(-1) for CoQ10H2 and 8.6-4292 ng mL(-1) for CoQ10. The limits of detection (LODs) were 7.0 and 1.0 ng mL(-1) and limits of quantification (LOQs) were 15.0 and 5.0 ng mL(-1) for CoQ10H2 and CoQ10, respectively. This rapid extractive and analytical method could avoid artificial auto-oxidation of the reduced form of CoQ10, enabling the native redox state assessment. This reliable method was also successfully applied for the measurement of the CoQ10 redox state in liver tissues of mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin, revealing the down-regulated mitochondrial electron transport chain.

High-accuracy analysis system for the redox status of coenzyme Q10 by online supercritical fluid extraction–supercritical fluid chromatography/mass spectrometry

The accurate profiling of oxidative stress markers is often disturbed by oxidation occurred during sample preparation. In this study, an online supercritical fluid extraction–supercritical fluid chromatography/mass spectrometry system was constructed utilizing supercritical fluid as an efficient solvent for extraction. A higher ratio of the reduced form of coenzyme Q10 (CoQ10) was detected by online extraction, rather than by offline extraction using a conventional organic solvent. The results suggest that the profile of easily oxidized compounds can be acquired with high accuracy using this system because the oxidation of the target compounds during sample preparation can be avoided when using the online extraction.

Altered redox status of coenzyme Q9 reflects mitochondrial electron transport chain deficiencies in Caenorhabditis elegans

Mitochondrial disorders are often associated with primary or secondary CoQ10 decrease. In clinical practice, Coenzyme Q10 (CoQ10) levels are measured to diagnose deficiencies and to direct and monitor supplemental therapy. CoQ10 is reduced by complex I or II and oxidized by complex III in the mitochondrial respiratory chain. Therefore, the ratio between the reduced (ubiquinol) and oxidized (ubiquinone) CoQ10 may provide clinically significant information in patients with mitochondrial electron transport chain (ETC) defects. Here, we exploit mutants of Caenorhabditis elegans ( C. elegans) with defined defects of the ETC to demonstrate an altered redox ratio in Coenzyme Q9 (CoQ9), the native quinone in these organisms. The percentage of reduced CoQ9 is decreased in complex I ( gas-1) and complex II ( mev-1) deficient animals, consistent with the diminished activity of these complexes that normally reduce CoQ9. As anticipated, reduced CoQ9 is increased in the complex III deficient mutant ( isp-1), since the oxidase activity of the complex is severely defective. These data provide proof of principle of our hypothesis that an altered redox status of CoQ may be present in respiratory complex deficiencies. The assessment of CoQ10 redox status in patients with mitochondrial disorders may be a simple and useful tool to uncover and monitor specific respiratory complex defects.

Environmental contaminants and redox status of coenzyme Q10 and vitamin E in Inuit from Nunavik

The Inuit are heavily exposed to potentially prooxidant contaminants such as methylmercury (MeHg) and polychlorinated biphenyls (PCB) through their traditional diet. This diet is also an abundant source of n-3 polyunsaturated fatty acids (n-3 PUFA), selenium, and antioxidants, which might reduce cardiovascular risk. Although Inuit from Nunavik have low concentrations of plasma oxidized low-density lipoprotein (OxLDL) and elevated glutathione-related antioxidant defenses, the variance in OxLDL was predicted by PCB and blood glutathione, leaving the issue of contaminant-associated oxidative stress unresolved. The objective of the study was to assess oxidative stress in these Inuit by measuring the plasma concentrations and redox states of α-tocopherol and coenzyme Q10 (CoQ10), 2 sensitive biomarkers of oxidative stress, in relation to exposure. Plasma lipophilic antioxidants were determined by high-performance liquid chromatography–coupled electrochemical detection; and their relations to PCB, MeHg, n-3 PUFA, selenium, and OxLDL were assessed by multivariate analyses. Ubiquinol-10, ubiquinone-10, and ubiquinone-10 to CoQ10 total ratio were elevated as compared with white populations but showed no associations with PCB, MeHg, or n-3 PUFA. Ubiquinol-10 ( β = .23, P = .007) and CoQ10 total ( β = .27, P = .009) were predicted by blood selenium; and α-tocopherol, by PCB ( β = 4.12, P = .0002), n-3 PUFA ( β = 9.16, P = .02), and OxLDL ( β = 3.04, P = .05). Unexpectedly, the α-tocopheryl quinone to α-tocopherol ratio, in the reference range, was negatively predicted by PCB ( β = −0.41, P = .02). Using sensitive biomarkers of redox alterations, we found no evidence for MeHg- or PCB-associated oxidative stress in these Inuit. However, despite robust blood antioxidant defenses, the unusually elevated ubiquinone-10 to CoQ10 total ratio (0.21 ± 0.11) suggests some form of oxidative stress of unknown origin.

Decreased Coenzyme Q10 Concentration in Plasma of Children with Cystic Fibrosis

Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic fibrosis might be diminished. Because these patients have increased oxidative stress due to chronic pulmonary inflammation, we also assumed that the oxidized form of CoQ10 might be relatively increased. The total plasma CoQ10 levels and the oxidized and reduced form were measured by high-performance liquid chromatography in 30 children with cystic fibrosis (mean FEV1 % predicted = 88.5% +/- 18.7%) and 30 age-matched controls. Total plasma CoQ10 levels were significantly lower in the cystic fibrosis group as compared with the control group (0.87 +/- 0.42 micromol/L and 1.35 +/- 0.39 micromol/L, respectively; P < 0.001). When correcting for the lower serum cholesterol level in patients with cystic fibrosis, this difference remained significant: the CoQ10/cholesterol ratio (micromol/mol) was 268.8 +/- 136.7 and 334.0 +/- 102.9 in patients and controls, respectively (P < 0.05). However, the CoQ10 redox status was identical in patients and controls (86.4% +/- 7.1% and 85.4% +/- 7.3%, respectively). We found that the overall plasma CoQ10 concentration is lower in patients with cystic fibrosis, probably because of fat malabsorption. The CoQ10 redox status was not disturbed, indicating that CoQ10 could still be adequately regenerated in this group of patients with cystic fibrosis with mild-to-moderate pulmonary disease.

Plasma levels and redox status of coenzyme Q10 in infants and children

Increased attention has been paid to the role of lipophilic antioxidants in childhood nutrition and diseases during recent years. The lipophilic antioxidant coenzyme Q10 (CoQ10) is known as an effective inhibitor of oxidative damage. In contrast to other lipophilic antioxidants like alpha-tocopherol the plasma concentrations of CoQ10 in childhood are poorly researched. The aim of this study was to determine plasma level and redox status (oxidized form in total CoQ10 in %) of CoQ10 in clinically healthy infants, preschoolers and school-aged children. Plasma level and redox status of CoQ10 were measured by HPLC in 199 clinically healthy children, three groups of infants [1st-4th month (n = 35), 5th-8th month (n = 25), 9th-12th month (n = 25) ], preschoolers (n = 60) and school-aged children (n = 54). The CoQ10 plasma levels were related to plasma cholesterol concentrations. The median and the 5th and 95th percentile were calculated. Plasma levels and redox status of CoQ10 in infants were significantly higher than in preschoolers and school-aged children. The CoQ10 redox status in the 1st-4th month was significantly increased when compared to the remaining subgroups of infants. In elder children the CoQ10 redox status stabilized. This is the first study concerning age-related values of plasma level and redox status of CoQ10 in apparently healthy children. Decreased CoQ10 values could be involved in various pathological conditions affecting childhood. Therefore, the application of age-adjusted reference values may provide more specific criteria to define threshold values for CoQ10 deficiency in plasma.

Oxidative Stress and Sleep Apnoea in Clinically Healthy Infants in the First Year of Life. Oxidativer Stress und Schlafapnoen bei klinisch gesunden Sauglingen

Respiratory instability as well as tissue damage by free radicals (oxidative stress) have been hypothesized to play a role in cases of sudden and unexpected infant death in the first year of life. The ratio of the oxidized/reduced form of redox compounds in the circulation could be used as a marker of oxidative stress. Therefore, the sleep apnoea rate and redox status of coenzyme Q10 (CoQ10) (percentage of the oxidized form in total CoQ10) were measured in a population of clinically healthy infants in their first year of life in order to study whether a physiological parameter of respiratory instability is related to a biochemical parameter of oxidative stress. Between May and December 1999, 323 infants in the first year of life were referred to a paediatric sleep laboratory. Sleep apnoea rate, periodic breathing and parameters of oxygenation (SaO2 and TcPO2) were calculated based on polysomnographic recordings. The CoQ10 redox status was calculated based on high-pressure liquid chromatographic (HPLC) analysis. Statistical analysis showed an age-dependent decrease in apnoea rate (r=−0.38) and CoQ10 redox status (r=−0.40). An increased CoQ10 redox status (median: 16.6%; range: 7.3–29.7%) was found in infants with high apnoea rates above the 90th percentile of a reference group in comparison with infants with apnoea rates below the 90th percentile of a reference group (median: 10.4%; range: 5.1–20.4%; P=0.031). These findings may indicate that high apnoea rates are accompanied by increased formation of free radicals in clinically healthy infants in the first year of life.

Altered redox state of platelet coenzyme Q10 in Parkinson's disease.

The reduced form of coenzyme Q10 (CoQ10) acts as a lipophilic antioxidant and participates in electron and proton transport of the respiratory chain in the inner mitochondrial membrane. An alteration in CoQ10 redox state may thus reflect a change in membrane electron transport and the effectiveness of defense against toxic reactive oxygen species such as hydrogen peroxide and superoxide. In Parkinson's disease alterations in the activities of complex I have been reported in substantia nigra and platelets. Deficiency of mitochondrial enzyme activities could affect electron transport which might be reflected by the platelet CoQ10 redox state. We have determined concentrations of the reduced and oxidized forms of CoQ10 and the activity of monoamine oxidase B in platelets isolated from parkinsonian patients and age- and gender-matched controls. Platelet CoQ10 redox ratios (reduced CoQ10 to oxidized CoQ10) and the ratio of the reduced form, compared with total platelet CoQ10, were significantly decreased in de novo parkinsonian patients. Platelet CoQ10 redox ratios were further decreased by L-DOPA treatment (not significant), whilst selegiline treatment partially restored CoQ10 redox ratios. Monoamine oxidase activities in non-selegiline treated patients were similar to controls. Our results either suggest an impairment of electron transport or a higher need for reduced forms of CoQ10 in the platelets of even de novo parkinsonian patients. However, the CoQ10 redox ratio was not correlated to disease severity, as determined by the Hoehn and Yahr PD disability classification, suggesting that this parameter may not be useful as a peripheral trait marker for the severity of PD but as an early state marker of PD.

The redox status of coenzyme Q10 in total LDL as an indicator of in vivo oxidative modification. Studies on subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1 versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 = .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were reduced compared with group 1 (P < .05). The K-value a measure of the LDL density, correlated with the the redox status (r = .37, P < .05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.

Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress.

It has been postulated that lipid peroxidation plays a crucial role in the pathogenesis of atherosclerosis. As CoQ10H2 (reduced form of coenzyme Q10) is easily oxidized to CoQ10 (oxidized form of coenzyme Q10), it has been proposed that the CoQ10H2/CoQ10 ratio may be used as a possible marker of in vivo oxidative stress. However, sample preparation has an important effect on the redox status of coenzyme Q10 due to the extreme sensitivity of CoQ10H2 towards oxidation. We now report a rapid, simple isocratic HPLC procedure for the determination of CoQ10H2 and CoQ10 in plasma isopropanol extracts, and we used this method to investigate conditions by which the CoQ10H2/CoQ10 ratio can be reliably measured. Our results indicate that CoQ10H2 is unstable in whole blood, plasma, and isopropanol extracts; subsequently the CoQ10H2/CoQ10 ratio changes considerably soon after a blood sample has been obtained. The time period since blood sampling and HPLC analysis, as well as the sample pretreatment procedure, are two factors that have a profound effect on the pre-analytical variation in the determination of the CoQ10H2/CoQ10 ratio. If these two factors are properly controlled, the CoQ10H2/CoQ10 ratio may be a sensitive and practical way to measure in vivo oxidative stress. Furthermore, this indicator is independent from plasma total cholesterol concentrations, implying that groups who differ with respect to cholesterol levels may be compared directly.