Coenzyme Q10 Levels Research Articles

Prenatal and progressive coenzyme Q10 administration to mitigate muscle dysfunction in mitochondrial disease.

ADCK genesencode aarF domain-containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult-onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid β-oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ10, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention. We used Adck2 heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests. We demonstrated that Adck2 heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). Adck2 heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ10 could mitigate these embryonic defects. Heterozygous Adck2 mice also showed a decrease in myogenic cell differentiation, with more severe consequences in 'aged' mice (41.63% smaller) (P<0.01). Consequently, heterozygous Adck2 mice displayed accelerated muscle wasting associated with ageing in muscle structure (P<0.05), muscle function (less grip strength capacity) (P<0.001) and muscle mitochondrial respiration (P<0.001). Furthermore, progressive CoQ10 administration conferred protective effects on mitochondrial function (P<0.0001) and skeletal muscle (P<0.05). Our work uncovered novel aspects of CoQ deficiencies, revealing defects during embryonic development in mammals for the first time. Additionally, we identified the gradual establishment and progression of the deleterious Adck2 mouse phenotype. Importantly, CoQ10 supplementation demonstrated a protective effect when initiated during development.

Reduced retinol (vitamin A) and α-tocopherol (vitamin E) blood levels and increased myeloperoxidase (MPO) activity in children with high myopia

The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = − 0.514 p < 0.001). Increased myeloperoxidase (MPO) activity (p < 0.018), and decreased concentrations of retinol (p < 0.001) and α-tocopherol (p < 0.023) in patients with HM and the axial length of the eye > 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p < 0.001, p < 0.021, respectively). Increased MPO activity in advanced stages of HM may confirm an inflammatory process in HM patients. Reduced retinol and α-tocopherol concentrations and their link to disease progression indicate a need for monitoring their levels and supplementation in children with HM.

Therapeutic Effects of Coenzyme Q10 in the Treatment of Ischemic Stroke.

Ischemic stroke is the second deadly disease worldwide, but current treatment is very limited. The brain, rich in lipids and high in oxygen consumption, is susceptible to damage from oxidative stress after ischemic stroke. Thus, antioxidants are promising neuroprotective agents for treatment and prevention of ischemic stroke. Coenzyme Q10 is the only lipophilic antioxidant that can be synthesized de novo by cells and plays a key role as an electron carrier in the oxidative phosphorylation of the mitochondrial electron transport chain. However, the reduced form of coenzyme Q10 (Ubiquinol) levels are significantly deficient in the brain. The aim of this article is to review the therapeutic effects and mechanisms of coenzyme Q10 in ischemic stroke. Current studies have found that coenzyme Q10 protects and treats ischemic stroke through multiple mechanisms based on the evidence from in vitro experiments, in vivo experiments, and clinical observations. For the first time, we reviewed the neuroprotective effects of coenzyme Q10 in ischemic stroke. Coenzyme Q10 exerts neuroprotective effects after ischemic stroke through anti-oxidative stress, anti-nitrosative stress, anti-inflammation, and anti-cell death. Here, we provided the evidence on the therapeutic and preventive effects of coenzyme Q10 in ischemic stroke and suggested the potential value of coenzyme Q10 as a medication candidate.

A Procedure for the Preparation of Some Natural Dietary Supplements Based on Coenzyme Q10 from Chicken Hearts and Oil Press Cakes

This study proposes a procedure for preparing some natural dietary supplements based on CoQ10 (coenzyme Q10) from lyophilised chicken hearts, respectively, oil press cakes of sunflower, rapeseed, walnut, and pumpkin. It consists of homogenising the powders obtained from these matrices with 2-propanol, succeeded by sonication, overnight maceration, collecting the liquid phase and filtering it under vacuum, removing the solvent by rotary evaporation, eliminating the 2-propanol traces under a nitrogen stream, and, finally, packaging in 10-mL amber glass bottles. Five dietary supplements were prepared using the above-described procedure and kept at room temperature for 9 months to evaluate their storage stability. To this end, CoQ10, TEAC (Trolox equivalent antioxidant capacity), and PV (peroxide value) levels were determined initially and every 3 months of storage. The highest levels of CoQ10 were found in the dietary supplements from lyophilised chicken hearts (18.12 mg/10 mL) and pumpkin press cakes (5.48 mg/10 mL). However, those from rapeseed and walnut press cakes had the highest levels of TEAC (19.23 µmol TE/g and 15.31 µmol TE/g, respectively). Exceeding the maximum permissible level for PV revealed a shelf-life of 3 months for the dietary supplements from pumpkin and walnut press cakes and less than that for the others.

Coenzyme Q10 and embryonic development: a potential role in reproductive medicine

Maternal mitochondria provide energy to the embryo through oxidative phosphorylation before blastocyst implantation, where intracellular energy is mainly supplied by glycolysis. Thus, it is obvious that mitochondria play a crucial role in providing energy for embryogenesis. Coenzyme Q10 (CoQ10) is a powerful endogenous membrane-localized antioxidant that protects circulating lipoproteins from lipid peroxidation. The results of several recent clinical studies have shown that exogenous CoQ10 supplements exert antioxidant effects and may be a potential therapy to reduce oxidative stress. CoQ10 deficiency increases the risk of impaired embryonic development; however, this relationship remains unclear. Given that the level of CoQ10 is influenced by enzymes involved in its synthesis, it is difficult to say whether the disorders are caused by CoQ10 deficiency or directly result from defects in the target gene. It has been shown that in the absence of CoQ10, ATP synthesis decreases in parallel with increased oxidative stress in mitochondria, two biological events which affect embryonic development. The review highlights the importance of CoQ10 as an antioxidant for improving egg quality, and also emphasizes its key role in embryonic development. It is necessary to conduct further studies aimed at studying metabolic changes during embryogenesis, as well as the mechanism of CoQ10 effects.

Modulation of toxic effects of ammonia on growth, pathology of liver and kidney tissues and relative expression of GH and IGF-1 Genes by CoQ10 Supplementation in Oncorhynchus mykiss.

Reducing the negative impact of environmental and stressful factors is a crucial step in achieving sustainable aquaculture. Therefore, a study was aimed at evaluating the impacts of Coenzyme Q10 (CoQ10) supplementation on growth, relative gene expression of Growth Hormone (GH) and Insulin-like growth factor-1 (IGF-1), liver and kidney histopathology against stress induced by ammonia in Rainbow trout (Oncorhynchus mykiss). The fish were given feed containing different levels of CoQ10 for 8 weeks: Control - CoQ10 0%, G1 - CoQ10 0.1%, G2 - CoQ10 0.5% and G3 - CoQ10 1%. At the end of the experiment, fish were exposed to ammonia stress concentration at 0.6mg/L for 24 h to assess liver and kidney tissue damage. Results showed that there was a significant activity increase in GH and IGF-1 genes due to supplementation with CoQ10 alone (p < 0.05). Gene expression for GH increased about two-fold whereas that for IGF-1 experienced a four-fold upregulation compared to controls (p < 0.05). CoQ10's-related antioxidant effects probably minimized liver and kidney cellular injuries, as significant decreases were observed in ammonia-induced mortality (p < 0.05). In summary, adding CoQ10 to the diet is a potential way to improve fish production through controlling the gene expression of GH and IGF-1, as well as making fish populations more resistant to possible future stress caused by ammonia in intensive or super-intensive aquaculture systems.

Breast cancer treatment with coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10) was identified in the late 1950s, and its potential role in cancer therapy appeared in the early 1960s when decreasing CoQ10 levels were found in some cancer patients. Breast cancer is a serious global health issue, and novel treatments are being developed. Its treatment is being investigated. CoQ10 has shown immune-boosting effects in clinical studies, encouraging researchers to look into its possible influence on breast cancer. Several research have looked at the link between CoQ10 and breast Coenzyme Q10 (CoQ10) was identified in the late 1950s, and its potential role in cancer therapy appeared in the early 1960s when decreasing CoQ10 levels were found in some cancer patients. Breast cancer is a serious global health issue, and novel treatments are being developed. Its treatment is being investigated. CoQ10 has shown immune-boosting effects in clinical studies, encouraging researchers to look into its possible influence on breast cancer. Several research have looked at the link between CoQ10 and breast cancer, focusing on its biological effects such as cytochrome c release and subsequent radical production. CoQ10 supplementation is commonly used by cancer patients to alleviate a perceived CoQ10 deficit associated with treatment-related toxicity. Notably, evidence shows that CoQ10 may be connected to lower tocopherol levels increasing the risk of breast cancer. However, bigger sample sizes, longer follow-up periods, and a better knowledge of the physiological role of circulating CoQ10 are required for a thorough assessment of CoQ10's possible role in breast cancer etiology. Antibacterial medications, therapy-induced adverse effects, and oxidative stress all have an impact on chemotherapy-related problems. Although CoQ10 has shown potential as an alternative breast cancer treatment, it is crucial to highlight that existing standard therapies, such as chemotherapy, radiation therapy, and hormone therapy, are not without their limitations. and targeted therapies are all options. Remain the cornerstone of breast cancer care. Always seek the most current and trustworthy information about breast cancer therapy from medical specialists.

Paramixta manurensis gen. nov., sp. nov., a novel member of the family Erwiniaceae producing indole-3-acetic acid isolated from mushroom compost

There are numerous species in the Erwiniaceae family that are important for agricultural and clinical purposes. Here we described the Erwiniaceae bacterium PD-1 isolated from mushroom (Pleurotus eryngii) compost. Comparative genomic and phylogenetic analyses showed that the strain PD-1 was assigned to a new genus and species, Paramixta manurensis gen. nov., sp. nov. in the family Erwiniaceae. From the average amino acid index, we identified the five AroBEKAC proteins in the shikimate pathway as a minimal set of molecular markers to reconstruct the phylogenetic tree of the Erwiniaceae species. The strain PD-1 containing annotated genes for ubiquinone and menaquinone produced a higher level of ubiquinone (Q8) than demethylmenaquinone (DMK8) and menaquinone (MK8) in anaerobic condition compared to aerobic condition, as similarly did the reference strains from the genera Mixta and Erwinia. Results from fatty acid methyl ester and numerical analyses of strain PD-1 showed a similarity to species of the genera Mixta and Winslowiella. This study revealed that the strain’s ability to utilize polyols, such as glycerol, erythritol, and d-arabitol, distinguished the strain PD-1 from the nearest relative and other type strains. The analyzed genetic markers and biochemical properties of the strain PD-1 suggest its potential role in the process of mushroom compost through the degradation of carbohydrates and polysaccharides derived from fungi and plants. Additionally, it can produce a high concentration of indole-3-acetic acid as a plant growth-promoting agent.

Effect of a Two-Week Diet without Meat and Poultry on Serum Coenzyme Q10 Levels

Coenzyme Q10 (CoQ10) is an essential compound for energy production in the mitochondria and the antioxidation of lipid-soluble substances in cells. As it can be biosynthesized in cells, CoQ10 is not an essential nutrient. However, its intake through meals contributes to the maintenance of CoQ10 levels in the body. Therefore, understanding the effects of daily diet on serum CoQ10 levels is crucial. This study investigated the effect of a two-week diet without meat or poultry, which are rich in CoQ10 content, on serum CoQ10 levels of 22 young women aged 20–21 years. Upon restricting the intake of meat and poultry, the participants’ average daily intake of CoQ10 from meals decreased from 2.1 ± 0.6 to 1.1 ± 0.5 mg/day. Simultaneously, the average serum reduced, oxidized, and total CoQ10 levels decreased by 14%, 31%, and 16%, respectively, after the two-week dietary intervention, whereas the reduced serum CoQ10 ratio increased significantly. These results suggest that meat and poultry are significant sources of CoQ10 in the diet. Dietary habits affect serum CoQ10 levels; however, further research is required to determine whether people who follow long-term diets with lower serum CoQ10 levels, such as a healthy reference diet proposed by the EAT-Lancet Commission in addition to vegetarian and vegan diets, need CoQ10 supplementation to maintain health and achieve healthy longevity.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Dietary co-enzyme Q10 boosted the growth performance, antioxidative capacity, immune responses, and intestinal and hepatic histomorphology of grey mullet (Liza ramada)

The aim of this experiment was to assess the potential benefits of supplementing coenzyme Q10 (CoQ10) in the diet of Liza ramada, with a focus on growth promotion, enhanced feed utilization, improved digestive enzyme activity, bolstered antioxidant defenses, and overall health. Five diets were prepared, maintaining consistent levels of lipids (7%) and protein (32%). These diets featured equivalent raw materials but varied in their CoQ10 content (0, 20, 40, 60, and 80 mg CoQ10/kg diet). Initial fish weight averaged 90.89±0.41 g, and each diet was administered to fish in triplicate tanks over a 60-day feeding period. Surprisingly, the diet with 80 mg/kg of CoQ10 showed the most substantial increases in weight gain (131.23±1.82 g), specific growth rate (1.40±0.01%/day), and a more favorable feed conversion ratio (1.73±0.01), outperforming the 60, 40, and 20 mg/kg CoQ10 diets. Additionally, 40 and 60 mg/kg CoQ10 diets demonstrated substantial improvements in digestive enzyme activity [protease (22.30±0.80 and 21.34±0.77, U/ mg), amylase (19.90±0.65 and 20.15±0.43, U/ mg), and lipase (27.04±0.80 and 27.41±0.87, U/ mg)], antioxidant markers [superoxide dismutase (14.01±0.27 and 14.44±0.62, U/ mg), catalase (1.19±0.04 and 1.20±0.04, U/ mg), and glutathione peroxidase (3.27±0.14 and 3.47±0.16, U/ mg)], and immune responses [lysozyme (302.12±3.18 and 294.25±7.64, U/ ml), bactericidal activity (5.00±0.04 and 6.03±0.14, U/ ml), respiratory burst using nitroblue tetrazolium (0.55±0.01 and 0.55±0.01, U/ ml), and alternative complement pathway activities (58.29±1.01 and 58.74±0.80, U/ ml)] in L. ramada (p < 0.05). Histological evaluations of the liver and intestine indicated structural enhancements, particularly in the 60 and 80 mg/kg CoQ10 groups, suggesting potential benefits for organ health. CoQ10 supplementation did not affect the survival rate and biochemical parameters [albumin, glucose, total protein, globulin, total cholesterol, triglyceride, AST, ALT, urea, and creatinine] (p > 0.05). These findings underscore the potential of CoQ10 as a valuable dietary additive to enhance the growth and overall health of L. ramada, with recommended inclusion levels of CoQ10 falling between 60 and 80 mg/kg.

Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Cre-ER(T)/fl mice by altering the coenzyme Q pool.

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43Cre-ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43fl/fl mice and Cx43Cre-ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia-reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165±0.338 vs. 4.18±0.55 nmol/mg protein, p<0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43Cre-ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate.

Rapid HPLC method reveals dynamic shifts in coenzyme Q redox state

Ubiquinol or coenzyme Q (CoQ) is a lipid-soluble electron carrier in the respiratory chain and an electron acceptor for various enzymes in metabolic pathways that intersect at this cofactor hub in the mitochondrial inner membrane. The reduced form of CoQ is an antioxidant, which protects against lipid peroxidation. In this study, we have optimized a UV-detected HPLC method for CoQ analysis from biological materials, which involves a rapid single-step extraction into n-propanol followed by direct sample injection onto a column. Using this method, we have measured the oxidized, reduced and total CoQ pools, and monitored shifts in the CoQ redox status in response to cell culture conditions and bioenergetic perturbations. We find that hypoxia or sulfide exposure induces a reductive shift in the intracellular CoQ pool. The effect of hypoxia is however, rapidly reversed by exposure to ambient air. Interventions at different loci in the electron transport chain can induce sizeable redox shifts in the oxidative or reductive direction, depending on whether they are up- or downstream of complex III. We have also used this method to confirm that CoQ levels are higher and more reduced in murine heart versus brain. In summary, the availability of a convenient HPLC-based method described herein, will facilitate studies on CoQ redox dynamics in response to environmental, nutritional and endogenous alterations.

Investigation of clinical effects of plasma coenzyme Q10 levels in COVID-19 patients in intensive care unit

Investigation of clinical effects of plasma coenzyme Q10 levels in COVID-19 patients in intensive care unit

Recovery response of coenzyme Q10 to exercise-related physiological muscle damage, inflammation and oxidative stress: A systematic review

This systematic review aims to demonstrate that coenzyme Q10 (CoQ10) supplementation may be an effective molecule in improving exercise performance and recovering muscle damage, improving antioxidant capacity, and suppressing inflammatory processes. The study covers the literature in PubMed, Google Scholar, Web of Science and Scopus databases from 2011 to 2023. The final review was conducted on June 6. In the literature analysis, eight keywords (exercise, oxidative stress, CoQ10, muscle damage, inflammation, skeletal muscle, heart muscle, and performance) were employed to investigate the publications. The full texts of 362 full texts of articles were included in this study. These were analyzed according to the PRISMA reporting criteria. In the analysis, one study was conducted with experimental animals, two studies were conducted with male and female participants, and 12 studies were conducted with only male participants. Participants in twelve studies were well-trained. However, two studies were conducted with a sedentary group. In addition, CoQ10 supplementation was present in all studies. CoQ10 supplementation was between 5-60 mg/kg in 4 studies and 100 mg/kg and above in the remaining 10 studies. Antioxidant capacities and inflammation markers were among the parameters of most interest. There were fewer studies on skeletal and cardiac muscle damage and performance markers. CoQ10 supplementation during intense exercise elevates plasma CoQ10 and antioxidant levels while reducing inflammation markers. Additionally, it enhances contractile function in sarcomeres and cardiomyocytes. Nevertheless, additional studies are necessary to comprehensively as certain CoQ10 impact on athletic performance.

Exploring mitochondrial biomarkers for Friedreich's ataxia: a multifaceted approach

This study presents an in-depth analysis of mitochondrial enzyme activities in Friedreich's ataxia (FA) patients, focusing on the Electron Transport Chain complexes I, II, and IV, the Krebs Cycle enzyme Citrate Synthase, and Coenzyme Q10 levels. It examines a cohort of 34 FA patients, comparing their mitochondrial enzyme activities and clinical parameters, including disease duration and cardiac markers, with those of 17 healthy controls. The findings reveal marked reductions in complexes II and, specifically, IV, highlighting mitochondrial impairment in FA. Additionally, elevated Neurofilament Light Chain levels and cardiomarkers were observed in FA patients. This research enhances our understanding of FA pathophysiology and suggests potential biomarkers for monitoring disease progression. The study underscores the need for further clinical trials to validate these findings, emphasizing the critical role of mitochondrial dysfunction in FA assessment and treatment.

Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers

Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, β-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. β-carotene was negatively correlated with adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). These results are promising, and the study is now being conducted on larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment.

GEMIN5 exerts key biological functions regulating pre-mRNAs intron removal to generate mature mRNAs. A series of patients were reported harboring mutations in GEMIN5. No treatments are currently available for this disease. We treated two of these patients with oral Coenzyme Q10 (CoQ10), which resulted in neurological improvements, although MRI abnormalities remained. Whole Exome Sequencing demonstrated compound heterozygosity at the GEMIN5 gene in both cases: Case one: p.Lys742* and p.Arg1016Cys; Case two: p.Arg1016Cys and p.Ser411Hisfs*6. Functional studies in fibroblasts revealed a decrease in CoQ10 biosynthesis compared to controls. Supplementation with exogenous CoQ10 restored it to control intracellular CoQ10 levels. Mitochondrial function was compromised, as indicated by the decrease in oxygen consumption, restored by CoQ10 supplementation. Transcriptomic analysis of GEMIN5 patients compared with controls showed general repression of genes involved in CoQ10 biosynthesis. In the rigor mortis defective flies, CoQ10 levels were decreased, and CoQ10 supplementation led to an improvement in the adult climbing assay performance, a reduction in the number of motionless flies, and partial restoration of survival. Overall, we report the association between GEMIN5 dysfunction and CoQ10 deficiency for the first time. This association opens the possibility of oral CoQ10 therapy, which is safe and has no observed side effects after long-term therapy.

Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway

BackgroundThe protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration.MethodsTo determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1β/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB).ResultsCompared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1β) signaling pathway.ConclusionsThese findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1β pathway in macrophages.Trial registrationDate of registration 09/04/2021 (number: ChiCTR2100045256).

Combination Therapy of Cuban Policosanol (Raydel®, 20 mg) and Intensive Exercise for 12 Weeks Resulted in Improvements in Obesity, Hypertension, and Dyslipidemia without a Decrease in Serum Coenzyme Q10: Enhancement of Lipoproteins Quality and Antioxidant Functionality in Obese Participants.

Obesity and overweight, frequently caused by a lack of exercise, are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and alleviates the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.1 ± 1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) reduced significantly up to around -15%, -13%, -33%, -11%, and -13%, respectively. In the serum lipid profile, at Week 12, a significant reduction was observed in the total cholesterol (TC) and triglyceride (TG) levels, up to -17% and -54% from the baseline, respectively. The serum HDL-C was elevated by approximately +12% from the baseline, as well as the percentage of HDL-C in TC, and HDL-C/TC (%), was enhanced by up to +32% at Week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold from the baseline in all participants at Week 12. In particular, the male participants exhibited a 1.4-fold increase from the baseline. The larger rise in serum CoQ10 was correlated with the larger increase in the serum HDL-C (r = 0.621, p = 0.018). The hepatic function parameters were improved; the serum γ-glutamyl transferase decreased at Week 12 by up to -55% (p < 0.007), while the aspartate aminotransferase and alanine transaminase levels diminished within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly with the reduction in TG content. The antioxidant abilities of HDL, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold and 1.6-fold at Week 12. The particle size and number of HDL were elevated up to +10% during the 12 weeks, with a remarkable decline in the TG content, glycation extent, and oxidation. The improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos, under the co-presence of carboxymethyllysine (CML), a pro-inflammatory molecule known to cause acute death. In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise displayed a significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment.