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Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells

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Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells

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Abstract

Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects. However, the molecular mechanisms to explain pleiotrophic effects of CoQ10 are not clear yet and it is likely that CoQ10 targets the expression of multiple genes. We therefore utilized gene expression profiling based on human oligonucleotide sequences to examine the expression in the human intestinal cell line CaCo-2 in relation to CoQ10 treatment. CoQ10 caused an increased expression of 694 genes at threshold-factor of 2.0 or more. Only one gene was down-regulated 1.5-2-fold. Real-time RT-PCR confirmed the differential expression for seven selected target genes. The identified genes encode proteins involved in cell signalling (n = 79), intermediary metabolism (n = 58), transport (n = 47), transcription control (n = 32), disease mutation (n = 24), phosphorylation (n = 19), embryonal development (n = 13) and binding (n = 9). In conclusion, these findings indicate a prominent role of CoQ10 as a potent gene regulator. The presently identified comprehensive list of genes regulated by CoQ10 may be used for further studies to identify the molecular mechanism of CoQ10 on gene expression.

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... Активність тільки одного гена зменшилася в 1,5-2 рази під впливом убіхінону. Виявлені гени кодують білки, що беруть участь у передачі клітинних сигналів, процесах метаболізму, транспорту, контролюють транскрипційні процеси й ембріональний розвиток, а також беруть участь у патогенезі різноманітних захворювань [13]. ...
... Окрім того, білок mgc3358, синтез якого модулюється убіхіноном, задіяний у розвитку хвороби Хаттінгтона. Також убіхінон здатен уповільнювати втрату дофамінових нейронів під час хвороби Паркінсона [13]. ...
... На рис. 2 схематично показано, як ці АФК здатні впливати на процеси транскрипції у клітині. Впливаючи на велику кількість генів із різноманітними функціями, убіхінон виступає як перспективний регулятор клітинних процесів [19,13]. ...
... Furthermore, CoQ10's role as anti-inflammatory molecule has been recently evaluated. CoQ10 modulates gene expression [25], covering anti-inflammatory functions, even though a clear mechanism is not fully understood [26,27]. CoQ10 anti-inflammatory activity has not been addressed yet in infertile males. ...
... After 3-5 days of sexual abstinence, semen samples were collected and placed at 37 • C for liquefaction. Standard semen analysis, according to the 2010 WHO laboratory manual for the examination and processing of human semen, 5th edition, has been performed [25]. The 65 patients were divided in 3 groups, as follows: ...
... C. Idiopathic oligo-, asteno-, oligoastenozoospermia (IDIO), 24 patients, median age and interquartile range 37 (33.5-40.5) years, BMI 24 (20)(21)(22)(23)(24)(25)(26)(27) kg/m 2 , 30% smokers. We used the term "idiopathic" referring to seminal abnormalities of unknown etiologies, according to literature indication [51][52][53][54]. ...
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Oxidative and inflammatory damage underlie several conditions related to male infertility, including varicocele. Free light chains of immunoglobulins (FLCs) are considered markers of low-grade inflammation in numerous diseases. Coenzyme Q10 (CoQ10), a lipidic antioxidant and anti-inflammatory compound, is involved in spermatozoa energy metabolism and motility. We aimed to evaluate FLCs’ seminal levels in patients with varicocele in comparison to control subjects and to correlate them with CoQ10 and Total Antioxidant Capacity (TAC) in human semen. Sixty-five patients were enrolled. Semen analysis was performed; patients were divided into three groups: controls, 12 normozoospermic patients, aged 34 (33–41) years; varicocele (VAR), 29 patients, aged 33 (26–37) years; and idiopathic, 24 oligo-, astheno- and oligoasthenozoospermic patients aged 37 (33.5–40.5) years. FLCs (κ and λ) were assayed by turbidimetric method; CoQ10 by HPLC; TAC by spectrophotometric method. λ FLCs showed a trend toward higher levels in VAR vs. controls and the idiopathic group. VAR showed a trend toward lower κ FLCs levels vs. the other two groups. When comparing κ/λ ratio, VAR showed significantly lower levels vs. controls and idiopathic. Moreover, CoQ10 seminal levels showed higher levels in VAR and idiopathic compared to controls. Data reported here confirm lower levels of κ/λ ratio in VAR and suggest a possible application in personalized medicine as clinical biomarkers for male infertility.
... Furthermore, dietary supplementation affecting CoQ10 levels has been shown in number of organisms to cause multiple phenotypic effects [12] Therefore, CO enzyme Q10 plays an www.wjpps.com 96% of all aerobically produced energy is produced by CoQ10. ...
... Coenzyme Q10 is the coenzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell. [12] In the current study, there were superior results for human sperm parameters post-thawing when using 10 µM CoQ10 than using 5 µM CoQ10. The main and principal factor is the direct and/indirect roles of CoQ10 on sperm plasma membrane, metabolism and physiology. ...
... In addition, mitochondrial dysfunction has also been proposed to change skeletal muscle innervation, leading to weakness and sarcopenia [15]. Coenzyme Q10 is a mitochondrial nutrient that acts as a transmitter of electrons in the mitochondria and is response for energy production [16]. Studies have observed that elderly individuals may suffer from a low level of coenzyme Q10, and this low level may be correlated with the incidence of sarcopenia [17][18][19][20]. ...
... Age could be a factor that causes the low concentration of coenzyme Q10 [20]. Coenzyme Q10 is a nutrient that participates in the process of energy production in mitochondria [15,16]. Coenzyme Q10 plays an important energy source that could help to increase glycogen synthesis and reserves in skeletal muscle [28]. ...
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The aim of this study was to explore the use of coenzyme Q10 and skeletal muscle protein biomarkers in the diagnosis of sarcopenia. Subjects with or without sarcopenia were recruited. The anthropometric, muscle strength and endurance measurements were assessed. Muscle proteins (albumin and creatine kinase), myokines (irisin and myostatin), and the coenzyme Q10 level were measured. Approximately half of the subjects suffered from a low coenzyme Q10 concentration (< 0.5 mM). The levels of creatinine kinase and irisin were significantly lower in subjects with sarcopenia (p £ 0.05). In receiver operating characteristic analyses, irisin and creatine kinase showed a better prediction capability for sarcopenia (area under the curve, irisin: 0.64 vs. creatinine kinase: 0.61) than other biomarkers. Additionally, a low level of irisin (< 118.0 ng/mL, odds ratio, 6.46, p < 0.01), creatine kinase (< 69.5 U/L, odds ratio, 3.31, p = 0.04), or coenzyme Q10 (< 0.67 mM, odds ratio, 9.79, p < 0.01) may increase the risk for sarcopenia even after adjusting for confounders. Since the levels of coenzyme Q10 and muscle biomarkers, such as irisin and creatine kinase, are associated with sarcopenia, we suggest they could be used as candidate markers to assist in the diagnosis of sarcopenia.
... CoQ10 supplementation has been shown to have epigenetic effects in genes involved with signaling, intermediary metabolism, transport, transcription control, disease mutation, phosphorylation, and embryonal development indicating a role in modulation of gene expression [22,23]. ...
... Other functions include modulation of the permeability transition pore, thus playing a role in apoptosis [28]. CoQ 10 s main functions are summarized in Figure 2. phosphorylation, and embryonal development indicating a role in modulation of gene expression [22,23]. In addition to its major function in the ETC, CoQ10 has an important anti-oxidant role stabilizing the plasma membrane and other intracellular membranes protecting membrane phospholipids from peroxidation [13]. ...
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The aging process includes impairment in mitochondrial function, a reduction in anti-oxidant activity, and an increase in oxidative stress, marked by an increase in reactive oxygen species (ROS) production. Oxidative damage to macromolecules including DNA and electron transport proteins likely increases ROS production resulting in further damage. This oxidative theory of cell aging is supported by the fact that diseases associated with the aging process are marked by increased oxidative stress. Coenzyme Q10 (CoQ10) levels fall with aging in the human but this is not seen in all species or all tissues. It is unknown whether lower CoQ10 levels have a part to play in aging and disease or whether it is an inconsequential cellular response to aging. Despite the current lay public interest in supplementing with CoQ10, there is currently not enough evidence to recommend CoQ10 supplementation as an anti-aging anti-oxidant therapy.
... Additionally, CoQ10, the only endogenously synthesized lipid-soluble antioxidant, prevents free-radical-induced oxidative damage to proteins, lipoproteins, mitochondrial DNA and cellular membranes [20]. Notably, beyond its antioxidant/radical-scavenging activity, CoQ10 may influence gene expression related to cell signaling, metabolism, nutrient transport [21] and inflammation [22]. Because of its pleiotropic functions with good safety and tolerance, CoQ10 may be useful as a nutritional supplement for a variety of pathological conditions, including neurodegenerative diseases [23]. ...
Article
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Coenzyme Q10 (CoQ10), a well-known antioxidant, has been explored as a treatment in several neurodegenerative diseases, but its utility in spinocerebellar ataxia type 3 (SCA3) has not been explored. Herein, the protective effect of CoQ10 was examined using a transgenic mouse model of SCA3 onset. These results demonstrated that a diet supplemented with CoQ10 significantly improved murine locomotion, revealed by rotarod and open-field tests, compared with untreated controls. Additionally, a histological analysis showed the stratification of cerebellar layers indistinguishable from that of wild-type littermates. The increased survival of Purkinje cells was reflected by the reduced abundance of TUNEL-positive nuclei and apoptosis markers of activated p53, as well as lower levels of cleaved caspase 3 and cleaved poly-ADP-ribose polymerase. CoQ10 effects were related to the facilitation of the autophagy-mediated clearance of mutant ataxin-3 protein, as evidenced by the increased expression of heat shock protein 27 and autophagic markers p62, Beclin-1 and LC3II. The expression of antioxidant enzymes heme oxygenase 1 (HO-1), glutathione peroxidase 1 (GPx1) and superoxide dismutase 1 (SOD1) and 2 (SOD2), but not of glutathione peroxidase 2 (GPx2), were restored in 84Q SCA3 mice treated with CoQ10 to levels even higher than those measured in wild-type control mice. Furthermore, CoQ10 treatment also prevented skeletal muscle weight loss and muscle atrophy in diseased mice, revealed by significantly increased muscle fiber area and upregulated muscle protein synthesis pathways. In summary, our results demonstrated biochemical and pharmacological bases for the possible use of CoQ10 in SCA3 therapy.
... Furthermore, the safety of CoQ10 is well documented in rats and humans [27,28]. e dosages chosen complied with dosages used in other in vitro studies [29][30][31][32]. 100 μM showed a significant change in most respiratory parameters and was therefore chosen for this study. CoQ10 carrier control in the same concentration as CoQ10 revealed no significant impact of the additives contained in QuinoMit Q10 fluid. ...
Article
The process of aging is characterized by the increase of age-associated disorders as well as severe diseases. Due to their role in the oxidative phosphorylation and thus the production of ATP which is crucial for many cellular processes, one reason for this could be found in the mitochondria. The accumulation of reactive oxygen species damaged mitochondrial DNA and proteins can induce mitochondrial dysfunction within the electron transport chain. According to the “mitochondrial theory of aging”, understanding the impact of harmful external influences on mitochondrial function is therefore essential for a better view on aging in general, but the measurement of mitochondrial respiration in skin cells from cell cultures cannot completely reflect the real situation in skin. Here, we describe a new method to measure the mitochondrial respiratory parameters in epithelial tissue derived from human skin biopsies using a XF24 extracellular flux analyzer to evaluate the effect of coenzyme Q10. We observed a decrease in mitochondrial respiration and ATP production with donor age corresponding to the “mitochondrial theory of aging”. For the first time ex vivo in human epidermis, we could show also a regeneration of mitochondrial respiratory parameters if the reduced form of coenzyme Q10, ubiquinol, was administered. In conclusion, an age-related decrease in mitochondrial respiration and ATP production was confirmed. Likewise, an increase in the respiratory parameters by the addition of coenzyme Q10 could also be shown. The fact that there is a significant effect of administered coenzyme Q10 on the respiratory parameters leads to the assumption that this is mainly caused by an increase in the electron transport chain. 'is method offers the possibility of testing age-dependent effects of various substances and their influence on the mitochondrial respiration parameters in human epithelial tissue.
... Numerous attempts have been made previously to lessen levels of oxidative stress during cerebral malaria; specifically it was shown that transient supplementation of SOD-1 which is an endogenous antioxidant protects against P. falciparum induced oxidative stress and apoptosis [18]. Coenzyme Q 10 is an essential cofactor in the bioenergetics reactions and a powerful antioxidant that acts against oxidative stress [66,67], and a regulator of gene expression [68]. These roles has resulted in Coenzyme Q 10 being investigated for treatment of neurodegenerative disorders, diabetes mellitus, and cardiovascular diseases [69][70][71]. ...
... Numerous attempts have been made previously to lessen levels of oxidative stress during cerebral malaria; specifically it was shown that transient supplementation of SOD-1 which is an endogenous antioxidant protects against P. falciparum induced oxidative stress and apoptosis [18]. Coenzyme Q 10 is an essential cofactor in the bioenergetics reactions and a powerful antioxidant that acts against oxidative stress [66,67], and a regulator of gene expression [68]. These roles has resulted in Coenzyme Q 10 being investigated for treatment of neurodegenerative disorders, diabetes mellitus, and cardiovascular diseases [69][70][71]. ...
Article
In animal model of experimental cerebral malaria (ECM), the genesis of neuropathology is associated with oxidative stress and inflammatory mediators. There is limited progress in the development of new approaches to the treatment of cerebral malaria. Here, we tested whether oral supplementation of Coenzyme Q 10 (CoQ 10 ) would offer protection against oxidative stress and brain associated inflammation following Plasmodium berghei ANKA (PbA) infection in C57BL/6 J mouse model. For this purpose, one group of C57BL/6 mice was used as control; second group of mice were orally supplemented with 200 mg/kg CoQ 10 and then infected with PbA and the third group was PbA infected alone. Clinical, biochemical, immunoblot and immunological features of ECM was monitored. We observed that oral administration of CoQ 10 for 1 month and after PbA infection was able to improve survival, significantly reduced oedema, TNF-α and MIP-1β gene expression in brain samples in PbA infected mice. The result also shows the ability of CoQ 10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ 10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ 10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ 10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ 10 as a candidate of antioxidant and immunomodulatory molecule in ECM and testing it in clinical studies either alone or in combination with antimalaria regimens to provide insight into a potential translatable therapy.
... In addition to direct antioxidant scavenging, CoQ10 regenerates vitamin E and ascorbate from their oxidized state [19]. CoQ10 supplementation has significant impact on the expression of many genes involved in cell signaling, metabolism, and transport [20]. Various diseases associated with CoQ10 deficiency can benefit from CoQ10 supplementation including cardiovascular and neurodegenerative diseases and cancer [21]. ...
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The main reasons for the inefficiency of standard glioblastoma (GBM) therapy are the occurrence of chemoresistance and the invasion of GBM cells into surrounding brain tissues. New therapeutic approaches obstructing these processes may provide substantial survival improvements. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) as a scavenger of reactive oxygen species (ROS) to increase sensitivity to temozolomide (TMZ) and suppress glioma cell invasion. To that end, we used a previously established TMZ-resistant RC6 rat glioma cell line, characterized by increased production of ROS, altered antioxidative capacity, and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic antiproliferative effect. These results were confirmed in a 3D model of microfluidic devices showing that the CoQ10 and TMZ combination is more cytotoxic to RC6 cells than TMZ monotherapy. In addition, cotreatment with TMZ increased expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential of the combined treatment was shown by gelatin degradation, Matrigel invasion, and 3D spheroid invasion assays as well as in animal models. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, our data provide evidences in favor of CoQ10 supplementation to standard GBM treatment due to its potential to inhibit GBM invasion through modulation of the antioxidant capacity.
... Also it has been reported that CoQ10 acts as a potent gene regulator and affects expression of genes involved in cell signalling, metabolism, transport, transcription control, disease mutation, phosphorylation, and embryonal development in human (Groneberg et al. 2005) and some of the effects of exogenously CoQ10 administration may be due to this property. ...
Article
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The main objective of current work was to determine the effects of low and high dose supplementation with coenzyme Q10 (CoQ10) on spatial learning and memory in rats with streptozotocin (STZ)-induced diabetes. Male Wistar rats (weighing 220 ± 10) were randomly divided into six groups: (i) Control (Con, n = 8); (ii) Control+ Low dose of CoQ10 (100 mg/kg) (CLD, n = 10); (iii) Control+ high dose of CoQ10 (600 mg/kg) (CHD, n = 10); (iv) Diabetic (D, n = 10); (v) Diabetic + Low dose of CoQ10 (100 mg/kg) (DLD, n = 10); (vi) Diabetic + high dose of CoQ10 (600 mg/kg) (DHD, n = 10). Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. CoQ10 was administered intragastrically by gavage once a day for 90 days. After 90 days, Morris water maze (MWM) task was used to evaluate the spatial learning and memory in rats. Diabetic animals showed a slower rate of acquisition with respect to the control animals [F (1, 51) = 92.81, P < 0.0001, two-way ANOVA]. High dose (but no low dose) supplementation with CoQ10 could attenuate deteriorative effect of diabetes on memory acquisition. Diabetic animals which received CoQ10 (600 mg/kg) show a considerable decrease in escape latency and traveled distance compared to diabetic animals (p < 0.05, two-way ANOVA,). The present study has shown that low dose supplementation with CoQ10 in diabetic rats failed to improve deficits in cognitive function but high dose supplementation with CoQ10 reversed diabetes-related declines in spatial learning.
... Earlier, Groneberg et al. studied the molecular mechanisms to explain the pleiotropic effects of CoQ10 on human CaCo -2 cells line. They stated that CoQ10 targets the expression of many genes involved in cell signaling, metabolism, embryonic development and nutrient transport [36]. Later on, in silico analysis suggested that signaling pathways of G-protein coupled receptors, JAK/ STAT, and Integrin contain a number of CoQ10 sensitive genes. ...
... Furthermore, the safety of CoQ10 is well documented in rats and humans [27,28]. e dosages chosen complied with dosages used in other in vitro studies [29][30][31][32]. 100 μM showed a significant change in most respiratory parameters and was therefore chosen for this study. CoQ10 carrier control in the same concentration as CoQ10 revealed no significant impact of the additives contained in QuinoMit Q10 fluid. ...
Article
Full-text available
The process of aging is characterized by the increase of age-associated disorders as well as severe diseases. Due to their role in the oxidative phosphorylation and thus the production of ATP which is crucial for many cellular processes, one reason for this could be found in the mitochondria. The accumulation of reactive oxygen species damaged mitochondrial DNA and proteins can induce mitochondrial dysfunction within the electron transport chain. According to the “mitochondrial theory of aging,” understanding the impact of harmful external influences on mitochondrial function is therefore essential for a better view on aging in general, but the measurement of mitochondrial respiration in skin cells from cell cultures cannot completely reflect the real situation in skin. Here, we describe a new method to measure the mitochondrial respiratory parameters in epithelial tissue derived from human skin biopsies using a XF24 extracellular flux analyzer to evaluate the effect of coenzyme Q10. We observed a decrease in mitochondrial respiration and ATP production with donor age corresponding to the “mitochondrial theory of aging.” For the first time ex vivo in human epidermis, we could show also a regeneration of mitochondrial respiratory parameters if the reduced form of coenzyme Q10, ubiquinol, was administered. In conclusion, an age-related decrease in mitochondrial respiration and ATP production was confirmed. Likewise, an increase in the respiratory parameters by the addition of coenzyme Q10 could also be shown. The fact that there is a significant effect of administered coenzyme Q10 on the respiratory parameters leads to the assumption that this is mainly caused by an increase in the electron transport chain. This method offers the possibility of testing age-dependent effects of various substances and their influence on the mitochondrial respiration parameters in human epithelial tissue.
... Coenzyme Q 10 is an endogenous lipophilic quinone that constitutes a key component of the mitochondrial respiratory chain but it is also present in other cellular sub-fractions and in plasma lipoproteins, where it exerts an important antioxidant role in synergism with vitamin E [21]. Moreover, it is also known to affect gene expression [22]. CoQ 10 role in sport nutrition has been investigated in several studies showing contrasting results. ...
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Objectives: Physical exercise significantly impacts the biochemistry of the organism. Ubiquinone is a key component of the mitochondrial respiratory chain and ubiquinol, its reduced and active form, is an emerging molecule in sport nutrition. The aim of this study was to evaluate the effect of ubiquinol supplementation on biochemical and oxidative stress indexes after an intense bout of exercise. Methods: 21 male young athletes (26 + 5 years of age) were randomized in two groups according to a double blind cross-over study, either supplemented with ubiquinol (200 mg/day) or placebo for 1 month. Blood was withdrawn before and after a single bout of intense exercise (40 min run at 85% maxHR). Physical performance, hematochemical parameters, ubiquinone/ubiquinol plasma content, intracellular reactive oxygen species (ROS) level, mitochondrial membrane depolarization, paraoxonase activity and oxidative DNA damage were analyzed. Results: A single bout of intense exercise produced a significant increase in most hematochemical indexes, in particular CK and Mb while, on the contrary, normalized coenzyme Q10 plasma content decreased significantly in all subjects. Ubiquinol supplementation prevented exercise-induced CoQ deprivation and decrease in paraoxonase activity. Moreover at a cellular level, in peripheral blood mononuclear cells, ubiquinol supplementation was associated with a significant decrease in cytosolic ROS while mitochondrial membrane potential and oxidative DNA damage remained unchanged. Discussion: Data highlights a very rapid dynamic of CoQ depletion following intense exercise underlying an increased demand by the organism. Ubiquinol supplementation minimized exercise-induced depletion and enhanced plasma and cellular antioxidant levels but it was not able to improve physical performance indexes or markers of muscular damage.
... Levels of CoQ10 can decrease both in acute and chronic illness leading to a decreased cellular energy production and to free radical overproduction. As dietary supplement, CoQ10 has low toxicity and does not induce serious adverse effects in humans [28,29]. As documented by Cordero and colleagues, the inflammasome complex activation and release of proinflammatory cytokines are implicated in the pathophysiology of fibromyalgia. ...
Article
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Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.
... Earlier, Groneberg et al. studied the molecular mechanisms to explain the pleiotropic effects of CoQ10 on human CaCo -2 cells line. They stated that CoQ10 targets the expression of many genes involved in cell signaling, metabolism, embryonic development and nutrient transport [36]. Later on, in silico analysis suggested that signaling pathways of G-protein coupled receptors, JAK/ STAT, and Integrin contain a number of CoQ10 sensitive genes. ...
Article
Background: Recurrent Miscarriage (RM) is one of the most frustrating clinical situations wherein most of the cases, neither the engaged obstetrician nor suffering couples know the exact etiology and cause of the disease. About 10-15% of women with RM diagnosed with antiphospholipid syndrome (APS) are characterized by the marked presence of antiphospholipid antibodies (aPLa). There are several scientific reports available on the association between APS and RM; however, scanty data available about the beneficial role of coenzyme Q10 (CoQ10) in APS and APS mediated RM. In the present attempt, we tried to gather information to explain the possible associations between the role of CoQ10 in RM and APS. Methods: We collected peer-reviewed literature using keywords; antiphospholipid syndrome, CoQ10, endothelial dysfunction, oxidative stress and recurrent miscarriage in online electronic databases, such as Web of Science, Science Direct, Google Scholar, PubMed and Medline. The qualitative analysis of content was done by summarizing interventions and findings of included studies, on the basis of which a conceptual framework was prepared for this narrative review. Results: The beneficial role of CoQ10 in diverse pathological conditions has been summarized and the evidence suggests that CoQ10 being a potent antioxidant helps in the amelioration of free radicalmediated aPLa production, endothelial damage and mitochondrial dysfunction. The supplementation of CoQ10 overcomes the immune dysregulation in idiopathic RM and APS; thus could be a possible therapeutic adjunct in such diseases. Conclusion: Based on this review, further comprehensive studies may be conducted to illuminate the beneficial therapeutic effects of supplementing CoQ10 on possible modifiable pathways involved in the progression of RM and APS.
... The mitochondrial cofactor coenzyme Q10 (CoQ10) or ubiquinone is a key component of the mitochondrial ETC and one of the most widely used natural supplements that target mitochondrial dysfunction (Mancuso et al. 2010;Orsucci et al. 2011;Potgieter et al. 2013;Rich and Marechal 2010). CoQ10 is also a strong antioxidant in its reduced form, and it can affect the expression of certain genes involved in cell signaling, metabolism and transport (Groneberg et al. 2005;Littarru and Tiano 2010). The main use of CoQ10 as a natural supplement has been to improve the efficiency of electron transfer between the various complexes of the ETC (Littarru and Tiano 2010;Mancuso et al. 2010). ...
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Mitochondria provide most of our cellular energy needs; therefore, mitochondrial dysfunction can cause fatigue and other symptoms that are commonly found in every chronic and many acute conditions. Reductions in mitochondrial function occur when there is loss of maintenance of inner mitochondrial membrane trans-membrane potential, modifications in the electron transport chain, damage to mitochondrial DNA, altered mitochondrial transcription, and reductions in the transport of critical substrates and metabolites into mitochondria. These events can result in reduced efficiency of oxidative phosphorylation and reductions in ATP production. Several components of mitochondria require routine replacement, and this can be facilitated with dietary changes and the use of natural supplements. Clinical trials have shown the utility of using oral mitochondrial replacement supplements, such as replacement glycerolphospholipids, l-carnitine, alpha-Lipoic acid, coenzyme Q10, NADH, pyrroloquinoline quinone and other mitochondrial supplements to improve mitochondrial function. Membrane Lipid Replacement supplements with or without other mitochondrial supplements can significantly diminish fatigue and other mitochondria-associated symptoms found in aging, cancer and chronic diseases.
... Lipid peroxidation, induced by oxygen radicals, results in cell membrane breakdown, which leads to inhibition of the sodium-potassium ATPase, cell swelling, and mitochondrial dysfunction [6]. As previously reported, CQ10 plays a key role in the mitochondrial respiratory chain by preventing oxidative stress injury to the mitochondrial membrane [29,30]. It is worth noting that there is a synergistic effect between Bax and Bak on mitochondrial fragmentation and perforation, cell apoptosis, and programmed cell death. ...
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Background: Oxidative stress and autophagy both play key roles in continuous cardiomyocyte death and cardiac dysfunction after reperfusion therapy for acute myocardial ischemia-reperfusion injury. Coenzyme Q10 (CQ10), which is a fat-soluble quinone antioxidant, is involved in the pathophysiological processes of neurodegenerative diseases, cancer, diabetes, heart failure, and other diseases. Our objective was to determine if, and by what mechanism, CQ10 can ameliorate acute myocardial ischemia-reperfusion injury and improve heart function. Methods and results: Fat-soluble CQ10 in soybean oil solvent was preconditioned in rats with acute myocardial ischemia-reperfusion injury by intraperitoneal injection. Oxidant and antioxidant levels were compared between the preconditioned and control groups. Autophagy was measured by Western blotting analysis of autophagy proteins. Proapoptotic proteins and immunofluorescence were used to assess cell apoptosis. Infarct size was determined by triphenyl tetrazolium chloride (TTC) staining and Evans blue staining and visualized myocardial pathology by tissue staining. Finally, we assessed cardiac function by electrocardiography (ECG) and hemodynamics. Conclusions: This study reveals that CQ10 preconditioning regulates antioxidant levels and the oxidant balance, enhances autophagy, reduces myocardial apoptosis and death, and improves cardiac function in rats with acute ischemia-reperfusion injury. These results imply that CQ10 protects against acute myocardial ischemia-reperfusion injury via the antioxidative stress and autophagy pathways.
... Coenzyme Q10 (CoQ10), also known as ubiquinone, ubidecarenone or coenzyme Q, is a lipid-soluble vitamin-like substance. It serves a role in the electron transport chain involved in the generation and regulation of cellular bioenergy (7,8). CoQ10 demonstrates bioenergetic and antioxidant properties (9). ...
Article
Coenzyme Q10 (CoQ10) is a fat‑soluble vitamin‑like substance used for the treatment of a variety of disorders, including osteoporosis. The exact mechanism underlying CoQ10‑mediated protection against osteoporosis remains to be elucidated. The present study aimed to evaluate the effect of CoQ10 on osteoblastic cell proliferation and differentiation, and therapeutic effects on a rat model of osteoporosis. Following treatment with different concentrations of CoQ10, cell proliferation and differentiation of rat bone marrow stromal cells (BMSCs), and expression of osteoblastogenic markers, were measured. Rats with osteoporosis subjected to ovariectomy (OVX) were treated with different concentrations of CoQ10. Serum levels of estrogen and bone metabolism markers were measured. Micro computed tomography scans were used to analyze morphological changes in bones. In addition, mRNA and protein levels of phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN)/phosphatidylinositol 4,5‑bisphosphate 3‑kinase (PI3K)/RAC‑alpha serine/threonine‑protein kinase(AKT), were determined. CoQ10 significantly increased the proliferation and osteogenic differentiation of BMSCs in a dose‑dependent manner, with an increased expression of osteogenic markers. CoQ10 significantly decreased bone resorption but exhibited no effect on serum E2 levels in vivo. CoQ10 markedly enhanced bone formation. Furthermore, the abundance of p‑PI3K and p‑AKT increased while PTEN levels decreased in a dose‑dependent manner following administration of CoQ10. CoQ10 stimulates the proliferation and differentiation of BMSCs and is effective for the treatment of OVX‑induced osteoporosis in rats. The above effects of CoQ10 may be mediated by activation of the PTEN/PI3K/AKT pathway.
... Finally, CoQ10 has been shown to influence the expression of a wide set of genes [240][241][242][243][244]. Modulation of inflammation described above represents a clear example where CoQ10 is able to influence the nuclear translocation of NF-κB. ...
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Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS) production and decreased antioxidant (AO) defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed.
... There is a close relationship between elevated detrusor muscle Cx43 expression and detrusor muscle overactivity [13]. Coenzyme Q10, CoQ10 or ubiquinone-10, is an endogenous compound that acts as a powerful antioxidant, a crucial cofactor in the mitochondrial electron transport system, as well as a modulator of gene expression [14,15]. CoQ10 tends to decrease both pro-inflammatory and oxidative stress markers in experimental animals [16,17]. ...
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Background: Competent detrusor muscles with coordinated contraction and relaxation are crucial for normal urinary bladder storage and emptying functions. Hence, detrusor instability, and subsequently bladder overactivity, may lead to undesirable outcomes including incontinence. Multiple mechanisms may underlie the pathogenesis of detrusor overactivity including inflammation and oxidative stress. Herein, we tested the possibility that CoQ10 may have a potential therapeutic role in detrusor overactivity. Methods: Forty adult male Wistar albino rats weighing 100-150 g were used in the present study. Rats were divided (10/group) into control (receiving vehicles), monosodium glutamate (MSG)-treated (receiving 5 mg/kg MSG daily for 15 consecutive days), MSG + OO-treated (receiving concomitantly 5 mg/kg MSG and olive oil for 15 consecutive days), MSG + CoQ10-treated (receiving concomitantly 5 mg/kg MSG and 100 mg/kg CoQ10 daily for 15 consecutive days) groups. Results: MSG resulted in significant increase in bladder weight and sensitised the bladder smooth muscles to acetylcholine. MSG has also resulted in significant increase in bladder TNF-α, IL-6, malondialdehyde, nerve growth factor and connexion 43, with significant decrease in the antioxidant enzymes superoxide dismutase and catalase. Olive oil had no effect on MSG induced alterations of different parameters. Treatment with CoQ10 has resulted in a significant restoration of all the altered parameters. Conclusion: Taken together, our results suggest that CoQ10 antagonizes the deleterious effects of MSG on detrusor activity. We propose that CoQ10 could be a therapeutic strategy targeting urinary bladder dysfunction.
... Therefore, blocking oxidative stress and apoptosis may be an effective therapeutic approach for SCI. Coenzyme Q10 (CoQ10) is a lipid-soluble vitamin-like benzoquinone compound that plays an important role in the mitochondrial respiratory chain [16,17]. Previous studies have shown that CoQ10 exerts its antioxidant and antiapoptotic effects in a variety of diseases, such as heart [18], nervous system [19] and reproductive system diseases [20], and cancer [21]. ...
Article
Spinal cord injury (SCI) is one of the most devastating diseases that may cause paralysis, disability and irreversible loss of functions, which ultimately lead to permanent disabilities and a decrease in patient life expectancy. Coenzyme Q10 (CoQ10) is a lipid-soluble vitamin-like benzoquinone compound that can exert antioxidant and anti-apoptotic functions in a variety of diseases. However, the antioxidant and anti-apoptotic effects of CoQ10 in the treatment of SCI are still unknown. Therefore, we designed experiments to measure the changes in antioxidant capacity (glutathione (GSH), superoxide dismutase (SOD) and the end product of lipid peroxidation (MDA)) and apoptosis products (Bax, Bcl-2 and Caspase-3) to evaluate the protective effects of CoQ10 on SCI and investigated whether CoQ10 exerts its functions through the Nrf-2/NQO-1 and NF-κB signaling pathway. Our results showed that CoQ10 treatment could significantly decrease the levels of oxidative products (MDA) and increase the activities of antioxidant enzymes (SOD and GSH) against oxidative stress, as well as decrease the levels of pro-apoptotic proteins (Bax and Caspase-3) and increase the levels of anti-apoptotic proteins (Bcl-2) against apoptosis after SCI. We also observed that CoQ10 exerted beneficial effects through the Nrf-2/NQO-1 and NF-κB signaling pathway. These findings suggested that CoQ10 had a protective effect by decreasing oxidative stress and apoptosis after SCI. Thus, our data may provide a new approach wherein CoQ10 may be considered as a potential effective therapeutic for the treatment of SCI.
... It is the only naturally occurring endogenous lipidsoluble antioxidant which, in its reduced and active form ubiquinol, may act as a direct free radical scavenger, inhibiting the oxidation of lipids, proteins and DNA [6] or may act synergistically with other antioxidants, such as vitamin E, regenerating its oxidised form, tocopheryl radical. CoQ10 also demonstrates a regulatory role in the expression of genes involved in cell signalling, metabolism and nutrition transport [7]. (1). ...
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Background: Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration. Method: The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed. Results: CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions. Conclusion: A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage.
... In non-tumor diseases, such as diabetes, kidney disease, and inflammation, COQ10 affects cell metabolism concerning cell transport, transcriptional regulation, and cell [19,20]. ...
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Objective: Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-15 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results: The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-15 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05). Conclusion: COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.
... CoQ10 is an endogenous antioxidant produced by the mevalonate pathway, which is important component of the mitochondrial respiratory chain. Multiple studies have shown that the regulatory role of CoQ10 in uncoupling proteins' activation (Parikh et al., 2009), cell signaling (Groneberg et al., 2005), cell growth (Crane, 1999), and cell death (Alleva et al., 2001). In recent research of ferroptosis with CoQ10, ferroptosis suppressor protein 1 (FSP1) has been recognized as an oxidoreductase of CoQ10 to reduce it at the plasma membrane and can strengthen the resistance of cells to ferroptosis (Bersuker et al., 2019). ...
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Background: Oxidative stress (OS) is associated with ferroptosis. Coenzyme Q10 (CoQ10), as an adjuvant treatment, has shown to be beneficial against OS. However, the efficacy of CoQ10 as a therapeutic agent against OS has not been promptly updated and systematically investigated. Methods: A systematic literature search was performed using the Medline, EMBASE, Web of science, Cochrane Central Register of Controlled Trials, CNKI, CBM, Science direct and clinical trial. gov to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. Results: Twenty-one randomized clinical studies met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation increased the levels of antioxidant enzymes [including superoxide dismutase (SOD) (SMD = 0.63; 95% CI: 0.38 to 0.88; p < 0.001), catalase (CAT) (SMD = 0.44; 95% CI:0.16 to 0.72; p = 0.002)] significantly and the levels of malondialdehyde (MDA) (SMD = -0.68; 95% CI: 0.93 to -0.43; p < 0.001) was decreased considerably. However, significant associations were not observed between this supplement and total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity. Conclusion: CoQ10 can improve OS as indicated by statistical significance in CAT and MDA concentrations, as well as SOD activity. Future studies focusing on long-term results and specific valuation of OS parameters are required to confirm the efficacy of CoQ10 on OS. We also believe that with the further research on ferroptosis, CoQ10 will gain more attention. Systematic Review Registration: [ https://inplasy.com/ ], identifier [INPLASY2021120123].
... Ubiquinol, meanwhile, presents antioxidant behavior in cell and organelle membranes. Apart from these main functions, CoQ 10 plays an important role in uncoupling proteins' activation [7], cell signaling [8], cell growth [9] and apoptosis through the modulation of the mitochondrial permeability transition pore [10]. This molecule has traditionally been used clinically as an enhancer of mitochondrial function or an antioxidant intended to either palliate or diminish the oxidative damage that may worsen the physiological outcome of a wide range of diseases. ...
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The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
... The reduced form of CoQ10, ubiquinol (UQH 2 ), prevents both the initiation and propagation of lipid peroxidation in cell membranes [81] and plasma lipoproteins. CoQ10 also regulates gene expression, especially of genes involved in the chronic inflammatory response, and exhibits anti-inflammatory properties [15,82,83]. Therefore, it seems clear that antioxidant integration is necessary to counteract the negative effects of age-related ROS accumulation. ...
Article
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Coenzyme Q (CoQ) is a key component of the respiratory chain of all eukaryotic cells. Its function is closely related to mitochondrial respiration, where it acts as an electron transporter. However, the cellular functions of coenzyme Q are multiple: it is present in all cell membranes, limiting the toxic effect of free radicals, it is a component of LDL, it is involved in the aging process, and its deficiency is linked to several diseases. Recently, it has been proposed that coenzyme Q contributes to suppressing ferroptosis, a type of iron-dependent programmed cell death characterized by lipid peroxidation. In this review, we report the latest hypotheses and theories analyzing the multiple functions of coenzyme Q. The complete knowledge of the various cellular CoQ functions is essential to provide a rational basis for its possible therapeutic use, not only in diseases characterized by primary CoQ deficiency, but also in large number of diseases in which its secondary deficiency has been found.
... CoQ also regulates gene expression [33]. Interestingly, many of the genes regulated are related with the inflammatory response [34,35] and can show anti-inflammatory properties [19]. ...
Article
Coenzyme Q (CoQ) is a key component for many essential metabolic and antioxidant activities in cells in mitochondria and cell membranes. Mitochondrial dysfunction is one of the hallmarks of aging and age-related diseases. Deprivation of CoQ during aging can be the cause or the consequence of this mitochondrial dysfunction. In any case, it seems clear that aging-associated CoQ deprivation accelerates mitochondrial dysfunction in these diseases. Non-genetic prolongevity interventions, including CoQ dietary supplementation, can increase CoQ levels in mitochondria and cell membranes improving mitochondrial activity and delaying cell and tissue deterioration by oxidative damage. In this review, we discuss the importance of CoQ deprivation in aging and age-related diseases and the effect of prolongevity interventions on CoQ levels and synthesis and CoQ-dependent antioxidant activities.
... Coenzyme Q10 as an important vitamin-like benzoquinone constituent involved in generating the cellular adenosine triphosphate in the respiratory chain of mitochondria and has positive impacts on numerous body functions, such as lowering blood pressure and CVDs (Kumar, Kaur, Devi, & Mohan, 2009), improving the health of highly complex energy-dependent organs (e.g., brain, heart, pancreas, liver, kidney, etc.; Bhagavan & Chopra, 2006), the wound healing by reducing oxidative stresses and increasing mitochondrial membrane potential (Yoneda et al., 2014), and promoting the membrane stability of genes coding the cell signaling, metabolism and growth (Groneberg et al., 2005). Although this lipidsoluble and high molecular weight (863.365 ...
Article
Encapsulation is a promising technological process enabling the protection of bioactive compounds against harsh storage, processing, and gastrointestinal tract (GIT) conditions. Legume proteins (LPs) are unique carriers that can efficiently encapsulate these unstable and highly reactive ingredients. Stable LPs‐based microcapsules loaded with active ingredients can thus develop to be embedded into processed functional foods. The recent advances in micro‐ and nanoencapsulation process of an extensive span of bioactive health‐promoting probiotics and chemical compounds such as marine and plant fatty acid‐rich oils, carotenoid pigments, vitamins, flavors, essential oils, phenolic and anthocyanin‐rich extracts, iron, and phytase by LPs as single wall materials were highlighted. A technical summary of the use of single LP‐based carriers in designing innovative delivery systems for natural bioactive molecules and probiotics was made. The encapsulation mechanisms, encapsulation efficiency, physicochemical and thermal stability, as well as the release and absorption behavior of bioactives were comprehensively discussed. Protein isolates and concentrates of soy and pea were the most common LPs to encapsulate nutraceuticals and probiotics. The microencapsulation of probiotics using LPs improved bacteria survivability, storage stability, and tolerance in the in vitro GIT conditions. Moreover, homogenization and high‐pressure pretreatments as well as enzymatic cross‐linking of LPs significantly modify their structure and functionality to better encapsulate the bioactive core materials. LPs can be attractive delivery devices for the controlled release and increased bioaccessibility of the main food‐grade bioactives.
... It is also involved in the regeneration of vitamin C and E [15]. Other CoQ10 functions include modulation of gene expression and involvement in inflammation and apoptosis [16][17][18][19]. ...
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The efficiency of coenzyme Q10 (CoQ10) supplements is closely associated with its content and stability in finished products. This study aimed to provide evidence-based information on the quality and stability of CoQ10 in dietary supplements and medicines. Therefore, ubiquinol, ubiquinone, and total CoQ10 contents were determined by a validated HPLC-UV method in 11 commercial products with defined or undefined CoQ10 form. Both forms were detected in almost all tested products, resulting in a total of CoQ10 content between 82% and 166% of the declared. Ubiquinol, ubiquinone, and total CoQ10 stability in these products were evaluated within three months of accelerated stability testing. Ubiquinol, which is recognized as the less stable form, was properly stabilized. Contrarily, ubiquinone degradation and/or reduction were observed during storage in almost all tested products. These reactions were also detected at ambient temperature within the products’ shelf-lives and confirmed in ubiquinone standard solutions. Ubiquinol, generated by ubiquinone reduction with vitamin C during soft-shell capsules’ storage, may lead to higher bioavailability and health outcomes. However, such conversion and inappropriate content in products, which specify ubiquinone, are unacceptable in terms of regulation. Therefore, proper CoQ10 stabilization through final formulations regardless of the used CoQ10 form is needed.
... Coenzyme Q10 (CoQ10), also known as ubiquinone, is a lipid-soluble antioxidant which plays a role in the electron transport chain involved in the generation and regulation of cellular bioenergy [418,419]. In contrast to other lipophilic antioxidants, CoQ10 stems from endogenous synthesis and food intake. ...
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The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nevertheless, exogenous stimuli of endogenous osteogenesis can be applied to promote the mineral apposition rate, bone formation, bone mass and bone strength, as well as expediting fracture repair and bone regeneration. The following review summarizes the latest studies related to the proliferation and differentiation of osteoblastic cells, enhanced by mechanical forces or supplemental signaling factors (such as trace metals, nutraceuticals, vitamins and exosomes), providing a thorough overview of the exogenous osteogenic agents which can be exploited to modulate and influence the mechanically induced anabolism of bone. Furthermore, this review aims to discuss the emerging role of extracellular stimuli in skeletal metabolism as well as their potential roles and provide new perspectives for the treatment of bone disorders.
... The view of all these functions, a deficiency in CoQ10 status could possibly contribute to the pathophysiology of neuropsychiatric and heart diseases, causing a failure in mitochondrial energetic metabolism and compromising cellular antioxidant capacity. A CoQ10 deficiency may also result from a genetic defect by biosynthesis, known as primary deficiency, or as a result of a mutation in a gene not directly involved in the biosynthesis of CoQ10, known as secondary deficiency (16)(17)(18). ...
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Nutritional psychiatry is a new area of research that seeks the relationship of nutrients in the brain axis and associated comorbidities. At the moment, there is an increasing discussion on the brain and heart axis seeking the understanding of the activity in reducing oxidative stress and mitochondrial respiratory chain, among the nutrients investigated is coenzyme Q10 (CoQ10). This important nutrient, which has a number of already established functions, has benefits in the treatment of psychiatric and heart disorders, it is believed to be the result of its antioxidant property and production of mitochondrial energy. However, there is a scarcity of studies on CoQ10 in the line of nutritional psychiatry, including there is still no consensus on the appropriate dosage or therapeutic plasmatic level of this nutrient. And this information is necessary both for the treatment of mitochondrial diseases and psychiatric and heart disorders. Therefore, this study seeks to describe the current knowledge about CoQ10 in the axis of nutritional psychiatry in the disordens brain and heart. Copyright © 2020, Thais de R. Bessa-Guerra et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... Furthermore, it is known that CoQ 10 participate in inflammation process, (14,15) apoptosis, (16,17) and gene expression. (18,19) In addition, several studies have demonstrated that CoQ 10 has broad therapeutic effects including diabetes, (20) cardiovascular disease, (21) and neurological disorder. (22) On the other hand, it also has been known that the intracellular CoQ 10 level decreases after the age of 20 years. ...
Article
Cellular senescence is an intricate and multifactorial phenomenon, which is characterized by an irreversible cellular growth arrest, it is caused in response to irretrievably DNA damage, telomere shorting, activation of oncogene, and oxidative stress. Human diploid fibroblasts are a well-established experimental model for premature senescence-related studies, and exposure of fibroblasts to H2O2 is widely used as a SIPS model. Recently, it has been reported many studies of CoQ10 as to anti-aging effects, however the effect of CoQ10 on H2O2-induced SIPS model of human skin fibroblasts has not been understood. So that, we investigated that human skin fibroblasts were used to investigate the prevention effect of CoQ10 against H2O2-induced SIPS model. We created SIPS model fibroblasts with treatment of 100 μM H2O2 for 2 h. In this study, CoQ10 also increased cell viability and mRNA levels of type I, IV collagen and protein level of type I collagen. Moreover, it is shown that CoQ10 suppressed oxidative stress, degradation of collagen by increasing MMP expression, and decreasing senescence-associated phenotypes (e.g. SA-βgal positive staining and SASP) for preventing skin aging via H2O2-induced SIPS model. These results suggested that CoQ10 has possibility to be contributory for extension of healthy life expectancy in Japan.
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The study examined the effect of endogenous lipid-soluble antioxidant coenzyme Q10 on the expression of UbiA gene of prenyltransferase domain-containing protein 1 (UbiAd1) involved in synthesis of vitamin K2 (and probably of coenzyme Q10) on a rat model of ischemic stroke provoked by ligation of the middle cerebral artery in the left hemisphere. Ischemia enhanced expression of mRNA of UbiAd1 gene in both cerebral hemispheres, but the effect was significant only in the contralateral one. The study revealed no effect of intraperitoneal injection of coenzyme Q10 (30 mg/kg) on ischemia-produced elevation of mRNA of UbiAd1 gene. Further studies are needed to assess possible neuroprotective effects of antioxidant coenzyme Q10.
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Benzoquinone and its reduced form hydroquinone belong to phenolic compounds and are found in living organisms in free form or in glycosides. They are active substances of some medicinal plants and have a pharmacological effect on the human body. Accordingly, their derivatives are important objects for chemical synthesis and development of new drugs. This article presents the findings of the structural design of substances with benzoquinone or hydroquinone fragment and sulfur-containing compound. By use of appropriate on-line programs a predictive screening of the biological activity and cytotoxicity of thiosulfonate derivatives of benzoquinone and hydroquinone has been conducted. It has been found that they have immense methodological potential to be synthesized by substances with a wide range of biological activities and a high value of probable activity, which substantiates the feasibility of conducting experimental studies on their biological activity, particularly anticancer.
Book
This book focuses on the use of various molecules with antioxidant properties in the treatment of major male genital tract disorders, especially male infertility, erectile dysfunction, and accessory gland infection. The coverage also includes discussion of pathophysiology, the molecular basis of male infertility, and the rationale for use of antioxidants, with particular attention to coenzyme Q10 and carnitine. Oxidative stress occurs when the production of reactive oxygen species, including free radicals, exceeds the body’s natural antioxidant defences, leading to cellular damage. Oxidative stress is present in about half of all infertile men, and reactive oxygen species can produce infertility both by damaging the sperm membrane, with consequences for sperm motility, and by altering the sperm DNA. There is consequently a clear rationale for the use of antioxidant treatments within andrology, and various in vitro and in vivo studies have indicated that many antioxidants indeed have beneficial impacts. In providing a detailed and up-to-date overview of the subject, this book will be of interest to both practitioners and researchers in andrology, endocrinology, and urology.
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Encapsulation technology is gaining attention across the world owing to its promising protection of active ingredients under hostile conditions. Various wall materials are used in the encapsulation of these sensitive ingredients. However, the legume proteins (LPs) are emerging and unique carriers for the delivery of bioactive owed to their biocompatibility, film formation and functional attributes. Legume proteins loaded with active ingredients can be used for the development of various functional foods. Modification strategies are making the legume proteins effective wall materials against various hostile conditions for the protection of probiotics and other sensitive ingredients. The present review describes the promising potential of legumes for the protection of active ingredients. Additionally, the effect of various modification processes on the functional properties of legumes has been reviewed.
Article
Oxidative stress owing to an imbalance between reactive oxygen species and antioxidants, such as coenzyme Q10 (CoQ10), is a major contributor to male infertility. We investigated the effects of the reduced form of CoQ10 (ubiquinol) supplementation on semen quality in dogs with poor semen quality. Three dogs received 100 mg of ubiquinol orally once daily for 12 weeks. Semen quality, serum testosterone, and seminal plasma superoxide dismutase (SOD) activity were examined at 2-week intervals from 2 weeks before ubiquinol supplementation to 4 weeks after the treatment. Ubiquinol improved sperm motility, reduced morphologically abnormal sperm, and increased seminal plasma SOD activity; however, it had no effect on testosterone level, semen volume, and sperm number. Ubiquinol supplementation could be used as a non-endocrine therapy for infertile dogs.
Chapter
Coenzyme Q10 (CoQ10) intake and supplementation has been directly and indirectly associated with physiological function relative to exercise, aging and reproduction. This chapter describes several significant aspects regarding biochemical properties and mechanism of action of CoQ10 in male and female fertility and reproduction. This effect is mainly through its action as an antioxidant, protecting against oxidative stress by controlling the levels of reactive oxygen species (ROS) associated with reproductive pathologies. Although some studies support the evidence of use of CoQ10 to improve fertility, the available literature is contradictory and conflicting due to lack of standardization regarding type, dosage and time frame of treatment with CoQ10 as well as the bio-specimen, the exercise protocol employed and the assays used to analyze these specimens. However, CoQ10 supplementation seems to be able to improve both male and female gamete physiology, conception and embryo development and pregnancy success, something that may be related to the protecting effect against ROS-related fertility issues. It seems it may, as well, attenuate somewhat the negative impact of age on fertility, though discontinuation of treatment will result in cessation or diminution of such effect.
Article
Background: High-quality of the oocyte is crucial for embryo development and the success of human assisted reproduction. The postovulatory aged oocytes lose the developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells, and has an important role in the mitochondrial respiration chain, against oxidative stress and modulation of gene expression. Objective: To investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging. Methods: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 μM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4. Results: Multiple CoQ10 biosynthesis enzymes are insufficient, and supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression. Conclusion: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4increase.
Article
Backgrounds and aims: Clinical studies demonstrated that the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapeutic agent in several neurological diseases such as Parkinson disease (PD), Huntington disease (HD), and migraine. The purpose of this study is to investigate oxidative stress effects, antioxidant enzymes activity, neuroinflammatory markers levels, and neurological outcome in acute ischemic stroke (AIS) patients following administration of CoQ10 (300 mg/day). Methods: Patients with AIS (n = 60) were randomly assigned to a placebo group (wheat starch, n = 30) or CoQ10-supplemented group (300 mg/day, n = 30). The intervention was administered for 4 weeks. Serum CoQ10 concentration, malondialdehyde (MDA), superoxide dismutase (SOD) activity, glial fibrillary acidic protein (GFAP) levels as primary outcomes and National Institute of Health Stroke Scale (NIHSS), Modified Ranking Scale (MRS), and Mini-Mental State Examination (MMSE) as secondary outcome were measured at the both beginning and end of the study. Results: Forty-four subjects with AIS completed the intervention study. A significant increase in CoQ10 level was observed in the supplement-treated group compared with placebo group (mean difference = 26.05 ± 26.63 ng/ml, 14.12 ± 14.69 ng/ml, respectively; P = 0.01), moreover CoQ10 supplementation improved NIHSS and MMSE scores significantly (P = 0.05, P = 0.03 respectively). but there were no statistically significant differences in MRS score, MDA, SOD, and GFAP levels between the two groups. Conclusions: CoQ10 probably due to low dose and short duration of supplementation, no favorable effects on MDA level, SOD activity and GFAP level.
Chapter
In this chapter we provide a review with a focus on the function of Coenzyme Q (CoQ, ubiquinone) in mitochondria. The notion of a mobile pool of CoQ in the lipid bilayer as the vehicle of electrons from respiratory complexes has somewhat changed with the discovery of respiratory supramolecular units, in particular the supercomplex comprising Complexes I and III; in such assembly the electron transfer is thought to be mediated by direct channelling, and we provide evidence for a kinetic advantage on the transfer based on random collisions. The CoQ pool, however, has a fundamental function in establishing a dissociation equilibrium with bound CoQ, besides being required for electron transfer from other dehydrogenases to Complex III. CoQ bound to Complex I and to Complex III is also involved in proton translocation; although the mechanism of the Q-cycle is well established for Complex III, the involvement of CoQ in proton translocation by Complex I is still debated. This review also briefly examines some additional roles of CoQ, such as the antioxidant effect of its reduced form and its postulated action at the transcriptional level.
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Acute myocardial infarction (AMI) is one of the leading causes of morbidity in the worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species (ROS), etc. One of the processes which is activated in response to I/R injury is autophagy. Indeed, autophagy acts as a “double-edged sword” in the pathology of myocardial I/R injury and there are controversial whether autophagy is beneficial or detrimental. Based on autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy. Keywords: Acute myocardial infarction, Ischemia/reperfusion injury, Autophagy.
Article
Coenzyme Q (CoQ) is a ubiquitous lipid serving essential cellular functions. It is the only component of the mitochondrial respiratory chain that can be exogenously absorbed. Here, we provide an overview of current knowledge, controversies, and open questions about CoQ intracellular and tissue distribution, in particular in brain and skeletal muscle. We discuss human neurological diseases and mouse models associated with secondary CoQ deficiency in these tissues and highlight pharmacokinetic and anatomical challenges in exogenous CoQ biodistribution, recent improvements in CoQ formulations and imaging, as well as alternative therapeutical strategies to CoQ supplementation. The last section proposes possible mechanisms underlying secondary CoQ deficiency in human diseases with emphasis on neurological and neuromuscular disorders.
Article
Objective The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10) supplementation on oxidative stress engendered from hypoxia in population live at high altitude. Methods This is an intervention study in which 50 females of volunteers population-36 of them who live at high altitude compared with the placebo group (14 from the total population that live at sea level). Blood samples were collected in -anticoagulant tubes from control and high altitude before and after CoQ10 supplementation (150 mg/day for 2, 4 and 8 weeks). Plasma was separated and used for the determination of malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), paraoxonase (PON1) by spectrophotometer, CoQ10 and vitamin E by high performance liquid chromatography (HPLC). Results Our results appeared that TAC, PON1, vitamin E and CoQ10 concentrations were significantly decreased in population at high altitude at base line compared to placebo group population at sea level. Whereas, administration of CoQ10 attenuated all measured parameters especially after eight weeks of administration. Conclusion We concluded that coenzyme Q10 supplement at a dose of 150 mg/day has a powerful effect in oxidative stress parameters and increased antioxidant parameters included vitamin E in population with hypoxia after 4 and 8 weeks. So that supplementation positively affects oxidative stress and is recommended CoQ10 supplementation in population who live at high altitude.
Article
Heart failure (HF) is one of the most common causes of death in Western society. Recent results underscore the utility of coenzyme Q10 (CoQ10) addition to standard medications in order to reduce mortality and to improve quality of life and functional capacity in chronic heart failure (CHF). The rationale for CoQ10 supplementation in CHF is two-fold. One is the well-known role of CoQ10 in myocardial bioenergetics, and the second is its antioxidant property. Redox balance is also improved by oral supplementation of CoQ10, and this effect contributes to enhanced endothelium-dependent relaxation. Previous reports have shown that CoQ10 concentration is decreased in myocardial tissue in CHF and by statin therapy, and the greater the CoQ10 deficiency the more severe is the cardiocirculatory impairment. In patients with CHF and hypercholesterolaemia being treated with statins, the combination of CoQ10 with a statin may be useful for two reasons: decreasing skeletal muscle injury and improving myocardial function. Ubiquinol, the active reduced form of CoQ10, presents higher bioavailability than the oxidised form ubiquinone, and should be the preferred form to be added to a statin. The combination ezetimibe/simvastatin may have advantages over single statins. Since ezetimibe reduces absorption of cholesterol and does not affect CoQ10 synthesis in the liver, the impact of this combination on CoQ10 tissue levels will be much less than that of high dose statin monotherapy at any target low density lipoprotein-cholesterol (LDL-C) level to be reached. This consideration makes the ezetimibe/statin combination the ideal LDL-lowering agent to be combined with ubiquinol in CHF patients. However, particular caution is advisable with the use of strategies of extreme lowering of cholesterol that may negatively impact on myocardial function. All in all there is a strong case for considering co-administration of ubiquinol with statin therapy in patients with depressed or borderline myocardial function.
Chapter
Coenzyme Q (CoQ) is required for normal metabolic functions in all tissues. In humans, the amount of this lipid increases in all organs during adolescence and reaches its highest peak during the first 2–3 decades of life. At 80 years of age, the amount is decreased to around half. This development is also observed in different regions of the brain. In rodents, a number of physical and chemical factors are known to increase CoQ in various organs. Depending on the type, duration and doses of the treatments applied, the amount of the lipid increased in different organs to variable extents. Vitamin E plays a regulatory role in CoQ synthesis. Low amount of vitamin E in the diet results in lower amount of CoQ in liver and blood, while high amount of this vitamin increase the amount. Several nuclear receptors are involved in the synthesis of the lipid. Mice knockout models of PPARα, RXRα, TRα, and LXRα receptors exhibit significantly reduced amounts of this lipid in the liver and spleen. The amount of CoQ increases in a number of rodent and human pathological conditions, while it decreases in human liver cancer and cardiomyopathy.
Article
Background: CoQ10 is a very important compound which is found in every tissue of our organism. It participates in the processes of cellular respiration and ATP production. Also, it acts as a strong antioxidant. In an organism, it is represented in two forms: oxidized (ubiquinone) and reduced (ubiquinol). Its low blood level may be a signal for a list of diseases. Materials and Methods: This study developed and compared two methods of CoQ10 determination in order to find the fastest and the most convenient one. The first one involved HPLC-UV with the wavelength of ubiquinone determination equivalent to 290 nm and 275 nm for ubiquinol, respectively. The second one was carried out on an HPLC/MS/MS system utilizing Electrospray Ionization (ESI) and triple quadrupole mass analyzer for quantification in MRM positive mode. Results: Two methods of ubiquinol and ubiquinone determination were developed and validated. HPLC-UV included sample preparation based on liquid-liquid extraction. The LLOQ was 0.50 µg/ml. HPLC-MS/MS method sample preparation was based on protein precipitation. The LLOQ was 0.10 µg/ml. Conclusion: During the investigation, a conclusion was drawn that the HPLC-UV method is too insensitive for simultaneous determination of ubiquinol and ubiquinone. Furthermore, ubiquinol is very unstable and during exogenous factors’ exposure, it rapidly turns into ubiquinone. While, the HPLCMS/ MS method turned out to be sensitive, selective, rapid as it provides an accurate determination of both forms of CoQ10 in spiked human plasma. Keywords: CoQ10, ubiquinone, ubiquinol, HPLC-UV, HPLC-MS/MS, human plasma.
Article
Coenzyme Q (CoQ) is an important component of the mitochondrial electron transport chain. The finding that multiple chronic diseases show lower levels of CoQ10 has led to the possibility that CoQ10 supplementation could be an effective approach to ameliorate or prevent disease progression. In this review, we discuss the state of the art regarding the role of CoQ10 in health and disease and describe the latest clinical studies which have tested the effects of CoQ10 supplementation in inflammatory diseases. The results of these studies indicate that individuals suffering from inflammation-related diseases show improvement under the CoQ10 supplementation protocol. However, these results have been inconsistent, leading to the need for additional studies at the preclinical and clinical levels, involving a greater number of subjects and different treatment regimes.
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The aim of our study was to investigate the relationships between the levels of coenzyme Q10 (CoQ10) and vitamin E and the levels of hydroperoxide in three subfractions of low density lipoproteins (LDL) that were isolated from healthy donors. LDL3, the densest of the three subfractions, has shown statistically significant lower levels of CoQ10 and vitamin E, which were associated with higher hydroperoxide levels when compared with the lighter counterparts. After CoQ10 supplementation, all three LDL subfractions had significantly increased CoQ10 levels. In particular, LDL3 showed the highest CoQ10 increase when compared with LDL1 and LDL2 and was associated with a significant decrease in hydroperoxide level. These results support the hypothesis that the CoQ10 endowment in subfractions of LDL affects their oxidizability, and they have important implications for the treatment of disease.
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Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.
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The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.
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Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells and form a subfamily of the mitochondrial carrier family. Physiological uncoupling of oxidative phosphorylation must be strongly regulated to avoid deterioration of the energy supply and cell death, which is caused by toxic uncouplers. However, an H+ transporting uncoupling function is well established only for UCP1 from brown adipose tissue, and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial. The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies made us seek a native UCP cofactor. Here we report the identification of coenzyme Q (ubiquinone) as such a cofactor. On addition of CoQ10 to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1. The H+ transport was highly sensitive to purine nucleotides, and activated only by oxidized but not reduced CoQ. H+ transport of native UCP1 correlated with the endogenous CoQ content.
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Based on the discovery of coenzyme Q (CoQ) as an obligatory cofactor for H(+) transport by uncoupling protein 1 (UCP1) [Echtay, K. S., Winkler, E. & Klingenberg, M. (2000) Nature (London) 408, 609-613] we show here that UCP2 and UCP3 are also highly active H(+) transporters and require CoQ and fatty acid for H(+) transport, which is inhibited by low concentrations of nucleotides. CoQ is proposed to facilitate injection of H(+) from fatty acid into UCP. Human UCP2 and 3 expressed in Escherichia coli inclusion bodies are solubilized, and by exchange of sarcosyl against digitonin, nucleotide binding as measured with 2'-O-[5-(dimethylamino)naphthalene-1-sulfonyl]-GTP can be restored. After reconstitution into vesicles, Cl(-) but no H(+) are transported. The addition of CoQ initiates H(+) transport in conjunction with fatty acids. This increase is fully sensitive to nucleotides. The rates are as high as with reconstituted UCP1 from mitochondria. Maximum activity is at a molar ratio of 1:300 of CoQ:phospholipid. In UCP2 as in UCP1, ATP is a stronger inhibitor than ADP, but in UCP3 ADP inhibits more strongly than ATP. Thus UCP2 and UCP3 are regulated differently by nucleotides, in line with their different physiological contexts. These results confirm the regulation of UCP2 and UCP3 by the same factors CoQ, fatty acids, and nucleotides as UCP1. They supersede reports that UCP2 and UCP3 may not be H(+) transporters.
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Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects cell membranes from oxidative damage and decreases apoptosis in leukemic cells cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2 (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum withdrawal induced an early increase of neutral-sphingomyelinase activity, release of ceramide, and activation of caspase-3 in both cell lines, but this effect was more pronounced in CEM cells. CoQ10 prevented activation of this cascade of events. Lipids extracted from serum-depleted cultures activated caspase-3 independently of the presence of mitochondria in cell-free in vitro assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by okadaic acid, indicating the implication of a phosphatase in this process. Our results support the hypothesis that plasma membrane CoQ10 regulate the initiation phase of serum withdrawal-induced apoptosis by preventing oxidative damage and thus avoiding activation of downstream effectors as neutral-sphingomyelinase and subsequent ceramide release and caspase activation pathways.
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Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson's disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson's disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the alpha-synuclein gene on chromosome 4 in the much more common sporadic, or 'idiopathic' form of Parkinson's disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson's disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson's disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of the brain, such as globus pallidus or cerebral cortex. Therefore, the specificity of mitochondrial impairment may play a role in the degeneration of nigrostriatal dopaminergic neurons. This view is supported by the fact that MPTP generating 1-methyl-4-phenylpyridine (MPP(+)) destroys dopaminergic neurons in the substantia nigra. Although the serum levels of CoQ10 is normal in patients with Parkinson's disease, CoQ10 is able to attenuate the MPTP-induced loss of striatal dopaminergic neurons.
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Ubiquinone (UQ) is a lipid found in most biological membranes and is a co-factor in many redox processes including the mitochondrial respiratory chain. UQ has been implicated in protection from oxidative stress and in the aging process. Consequently, it is used as a dietary supplement and to treat mitochondrial diseases. Mutants of the clk-1 gene of the nematode Caenorhabditis elegans are fertile and have an increased life span, although they do not produce UQ but instead accumulate a biosynthetic intermediate, demethoxyubiquinone (DMQ). DMQ appears capable to partially replace UQ for respiration in vivo and in vitro. We have produced a vertebrate model of cells and tissues devoid of UQ by generating a knockout mutation of the murine orthologue of clk-1(mclk1). We find that mclk1−/− embryonic stem cells and embryos accumulate DMQ instead of UQ. As in the nematode mutant, the activity of the mitochondrial respiratory chain of −/− embryonic stem cells is only mildly affected (65% of wild-type oxygen consumption). However, mclk1−/− embryos arrest development at midgestation, although earlier developmental stages appear normal. These findings indicate that UQ is necessary for vertebrate embryonic development but suggest that mitochondrial respiration is not the function for which UQ is essential when DMQ is present.
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Coenzyme Q (CoQ) is the key factor for the activity of the eukaryotic plasma membrane electron transport chain. Consequently, CoQ is essential in the cellular response against redox changes affecting this membrane. Serum withdrawal induces a mild oxidative stress, which produces lipid peroxidation in membranes. In fact, apoptosis induced by serum withdrawal can be prevented by several antioxidants including CoQ. Also, CoQ can maintain cell growth in serum-limiting conditions, whereas plasma membrane redox system (PMRS) inhibitors such as capsaicin, which compete with CoQ, inhibit cell growth and induce apoptosis. To understand how plasma membrane CoQ prevents oxidative stress-induced apoptosis we have studied the induction of apoptosis by serum withdrawal in CEM cells and its modulation by CoQ. Serum-withdrawal activates neutral sphingomyelinase (N-SMase), ceramide release and caspase-3-related proteases. CoQ addition to serum-free cultures inhibited a 60% N-SMase activation, an 80% ceramide release, and a 50% caspase-3 activity induced by serum deprivation. Caspase activation dependent on ceramide release since C2-ceramide was only able to mimic this effect in 10% foetal calf serum cultured cells but not in serum-free cultures. Also, in vitro experiments demonstrated that C2-ceramide and ceramide-rich lipid extracts directly activated caspase-3. Taken together, our results indicate that CoQ protects plasma membrane components and controls stress-mediated lipid signals by its participation in the PMRS.
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Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial. Academic movement disorders clinics. Eighty subjects with early PD who did not require treatment for their disability. Random assignment to placebo or coenzyme Q10 at dosages of 300, 600, or 1200 mg/d. The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit. The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300-mg/d group, +10.82 for the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was.09, which met our prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1200-mg/d and placebo groups was significant (P =.04). Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.
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Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects. Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention. The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia. Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks. We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes. Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345). These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes. This study was supported by a grant from the NH&MRC, Australia.
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Zinc deficiency affects hepatic functions and due to the central role of the liver in metabolism, this may contribute to metabolic alterations in other tissues in zinc deficiency. In addition to clinical manifestations of zinc deficiency, we used cDNA- and oligonucleotide-arrays to compare the expression of > 2500 different genes in liver of rats force-fed a zinc-adequate or a zinc-deficient diet for 11 d. Radio- or fluorescence-labeled cDNAs from liver of control and zinc-deficient rats were hybridized to arrays. Approximately 1550 mRNAs were detected above background levels; by comparing expression profiles of the two groups, the mRNA levels of 66 genes were found to be altered by zinc deficiency. Steady-state expression levels of 35 genes were reduced, whereas the mRNA-levels of 31 genes were elevated. Array data were verified by Northern blot analysis for 24 selected genes and 19 were confirmed to be up- or down-regulated. Among those, predominantly gene products that participate in growth (i.e., insulin-like growth factor binding proteins), lipid metabolism (long-chain acyl-CoA synthetase), xenobiotic metabolism (cytochrome P(450) isoenzymes), the stress response (glutathione transferase), nitrogen metabolism (cytosolic aspartate aminotransferase), intracellular trafficking (syntaxin isoforms) and signal transduction (G-protein-coupled receptors) were identified. Additionally, regulation of mRNA levels of genes important for porphyrin synthesis and collagen metabolism was observed. In conclusion, we have identified in vivo a number of mammalian genes from different cellular pathways whose expression changes in response to zinc depletion. The characterization of the identified genes and their products will allow a more comprehensive analysis of the role of zinc in metabolism; moreover, the mRNAs identified could be useful in establishing biomarkers for the determination of zinc status in mammals.
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Résumé La vitamine E, l'antioxydant liposoluble le plus important, fut découverte à l'Université de Californie à Berkeley en 1922. Depuis sa découverte, les études sur les tocophérols et les tocotrienols que constitue cette vitamine, ont été centrées pour la plupart sur leurs propriétés antioxydantes. En 1991, le groupe de Angelo Azzi (Boscoboinik et al . 1991 a,b ) fut le premier à décrire les fonctions autres que les antioxydantes et de transmission de signaux de l'α-tocophérol, en démontrant la régulation par la vitamine E de l'activité de la protéine kinase C dans les cellules de muscle lisse. Au niveau de la transcription, l'²-tocophérol module l'expression de la protéine de transfert hépatique de l'α-tocophérol, ainsi que l'expression du ge`ne alpha1 du collage`ne du foie, du ge`ne de la collagénase et du ge`ne de l'α-tropomyosine. Récemment, un facteur de transcription dépendant du tocophérol (la protéine associée au tocophérol) a été découvert. Il a été démontré sur des cellules cultivées que la vitamine E inhibe l'inflammation, l'adhésion cellulaire, l'agrégation des plaquettes et la prolifération des cellules de muscle lisse. Les avancées récentes de la biologie moléculaire et des techniques génomiques ont conduit à la découverte de nouveaux ge`nes et des mécanismes de transduction des signaux sensibles à la vitamine E.
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Antioxidants have concentration-dependent neuroprotective and proapoptotic activities in models of Parkinson's disease. The aim of our study was to determine gene-protein pathways of the antioxidants, dopamine (DA), R-apomorphine (R-APO), melatonin, and green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), in neuroblastoma cells, using a customized cDNA microarray and quantitative reverse transcriptase-polymerase chain reaction gene expression techniques. We demonstrate a concentration-dependent correlation between these compounds and modulation of cell survival/cell death-related gene pathways. High toxic concentration of DA (500 microM), R-APO (50 microM), melatonin (50 microM), and EGCG (50 microM) exhibited a similar profile of proapoptotic gene expression, increasing the level of bax, caspase-6, fas ligand, and the cell-cycle inhibitor gadd45 genes, while decreasing antiapoptotic bcl-2 and bcl-xL. Conversely, the low neuroprotective concentrations (1-10 microM) of these compounds induced an antiapoptotic response. Melatonin displayed an extremely low index of mortality, which may be partially explained by the observation that a high concentration did not significantly affect the expression of mitochondrial Bcl-2 family members, bcl-2 and bax. Protein analysis of Bcl-2, Bax, and activated caspase-3 correlated with the gene expression pattern. Our results provide for the first time new insights into the molecular events involved in the dose-dependent neuroprotective and neurotoxic activities of catechols and indole amine compounds.
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The brief review presents evidence that, in addition to the well-known functions of ubiquinone (coenzyme Q) as a component of the mitochondrial respiratory chain, this compound in the reduced form (ubiquinol) functions as an antioxidant. Ubiquinone in a partially reduced form is found in all cell membranes. It protects efficiently not only membrane phospholipids from peroxidation but also mitochondrial DNA and membrane proteins from free-radical-induced oxidative damage. This protective role of ubiquinol is independent of the effect of exogenous antioxidants, such as vitamin E, and it can both prevent the formation of free lipid radicals and eliminate them either directly or by regenerating vitamin E.
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Mice having a hereditary muscular dystrophy were curatively treated with coenzyme Q7 beginning in the fifth month of their life-span of eight months. The diet and animal management provided uniform groups for therapy for over two years. Therapy with CoQ7 increased survival to twice that of the control group in days from the onset of therapy to death and increased life-span to ten months. During therapy, physical performance initially improved, but later declined and death ensued. Dystrophic mice, as controls, only declined in physical performance to death. CoQ7 was isolated from the mitochondria from hearts and hind leg muscles of the orally treated mice. It appears that CoQ7 is substituting for and correcting the deficiency of CoQ9 in the dystrophic mice.
Article
The vital role of coenzyme Q in mitochondrial electron transfer and its regulation, and in energy conservation, is well established. However, the role of coenzyme Q in free oxyradical formation and as an antioxidant remains controversial. Demonstration of the existence of the semiquinone form of coenzyme Q during electron transport, coupled with recent evidence that hydrogen peroxide (but not molecular oxygen) may act as an oxidant of the semiquinone, suggests that the highly reactive OH. radical may be formed from the semiquinone. On the other hand, data exist implicating the Fe-S species as the source of electron transfer chain, free radical production. Additional data exist suggesting instead that the unpaired electron of the coenzyme Q semiquinone most likely dismutases superoxide radicals. These concepts and those arising from observations at several levels of organization including subcellular systems, intact animals, and human subjects in the clinical setting, supporting the concept of reduced coenzyme Q as an antioxidant, will be presented. The results of recent studies on the interaction between the two-electron quinone reductase--DT diaphorase and coenzyme Q10 will be presented. The possibility that superoxide dismutase may interact with reduced coenzyme Q, in conjunction with DT diaphorase inhibiting its autoxidation, will be described. The regulation of cellular coenzyme Q concentrations during oxidative stress accompanying aerobic exercise, resulting in increased protection from free radical damage, will also be presented.
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Many CoQ trials for mitochondrial encephalomyopathy are reported, however, the action of CoQ in the central nervous system is unknown. We administered CoQ to a patient with MELAS, and decreasing CSF lactate and pyruvate levels were revealed. This reduction in CSF lactate and pyruvate may be evidence that CoQ acts directly on the CNS. There have been no other descriptions of evidence of CoQ effective action in the central nervous system, a finding unique to this report.
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The muscle mitochondria of a patient with Kearns-Sayre/chronic external ophthalmoplegia plus syndrome were found to be completely deficient in respiratory complex I activity and partially deficient in complex IV and V activities. Treatment of the patient with coenzyme Q10 and succinate resulted in clinical improvement of respiratory function, consistent with the respiratory deficiencies. Restriction enzyme analysis of the muscle mtDNA revealed a 4.9-kilobase deletion in 50% of the mtDNA molecules. Polymerase chain reaction analysis demonstrated that the deletion was present in the patient's muscle but not in her lymphocytes or platelets. Furthermore, the deletion was not present in the muscle or platelets of two sisters. Hence, the mutation probably occurred in the patient's somatic cells. Direct sequencing of polymerase chain reaction-amplified DNA revealed a 4977-base-pair deletion removing four genes for subunits of complex I, one gene for complex IV, two genes for complex V, and five genes for tRNAs, which paralleled the respiratory enzymes affected in the disease. A 13-base-pair direct repeat was observed upstream from both breakpoints. Relative to the direction of heavy-strand replication, the first repeat was retained and the second repeat was deleted, suggesting a slip-replication mechanism. Sequence analysis of the human mtDNA revealed many direct repeats of 10 base pairs or greater, indicating that this mechanism could account for other reported deletions. We postulate that the prevalence of direct repeats in the mtDNA is a consequence of the guanine-cytosine bias of the heavy and light strands.
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We tested the efficacy of coenzyme Q10 (ubidecarenone, CoQ10) therapy in patients with Kearns-Sayre syndrome and other mitochondrial myopathies with chronic progressive external ophthalmoplegia (CPEO). We treated seven patients for 1 year with daily oral administration of 120 mg of CoQ10. Throughout the treatment most of our patients showed a progressive reduction of serum lactate and pyruvate levels following standard muscle exercise and generally improved neurologic functions. The ECG and echocardiogram showed no significant changes in our patients. None of our patients showed any improvement in ptosis and CPEO.
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This presentation is a brief review of current knowledge concerning some biochemical, physiological and medical aspects of the function of ubiquinone (coenzyme Q) in mammalian organisms. In addition to its well-established function as a component of the mitochondrial respiratory chain, ubiquinone has in recent years acquired increasing attention with regard to its function in the reduced form (ubiquinol) as an antioxidant. Ubiquinone, partly in the reduced form, occurs in all cellular membranes as well as in blood serum and in serum lipoproteins. Ubiquinol efficiently protects membrane phospholipids and serum low-density lipoprotein from lipid peroxidation, and, as recent data indicate, also mitochondrial membrane proteins and DNA from free-radical induced oxidative damage. These effects of ubiquinol are independent of those of exogenous antioxidants, such as vitamin E, although ubiquinol can also potentiate the effect of vitamin E by regenerating it from its oxidized form. Tissue ubiquinone levels are regulated through the mevalonate pathway, increasing upon various forms of oxidative stress, and decreasing during aging. Drugs inhibiting cholesterol biosynthesis via the mevalonate pathway may inhibit or stimulate ubiquinone biosynthesis, depending on their site of action. Administration of ubiquinone as a dietary supplement seems to lead primarily to increased serum levels, which may account for most of the reported beneficial effects of ubiquinone intake in various instances of experimental and clinical medicine.
Article
In order to evaluate different mitochondrial antioxidant systems, the depletion of alpha-tocopherol and the levels of the reduced and oxidized forms of CoQ were measured in rat liver mitochondria during Fe++/ascorbate and NADPH/ADP/Fe++ induced lipid peroxidation. During the induction phase of malondialdehyde formation, alpha-tocopherol declined moderately to about 80% of initial contents, whereas the total CoQ pool remained nearly unchanged, but reduced CoQ9 continuously declined. At the start of massive malondialdehyde formation, CoQ9 reaches its fully oxidized state. At the same time alpha-tocopherol starts to decline steeply, but never becomes fully exhausted in both experimental systems. Evidently the oxidation of the CoQ9 pool constitutes a prerequisite for the onset of massive lipid peroxidation in mitochondria and for the subsequent depletion of alpha-tocopherol. Trapping of the GSH by addition of dinitrochlorbenzene (a substrate of the GSH transferase), results in a moderate acceleration of lipid peroxidation, but alpha-tocopherol and ubiquinol levels remained unchanged when compared with the controls. Addition of succinate to GSH depleted mitochondria effectively suppressed MDA formation as well as alpha-tocopherol and ubiquinol depletion. The data support the assumption that the protective effect of respiratory substrates against lipid peroxidation in the absence of mitochondrial GSH is mediated by the regeneration of the lipid soluble antioxidants CoQ and alpha-tocopherol.
Article
Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.
It has been suggested that ubiquinone improves exercise performance and antioxidant capacity. We studied the effects of ubiquinone supplementation (120 mg.day-1 for 6 weeks) on aerobic capacity and lipid peroxidation during exercise in 11 young (aged 22-38 years) and 8 older (aged 60-74 years), trained men. The cross-over study was double-blind and placebo-controlled. Serum ubiquinone concentration increased after supplementation (P < 0.0001 for treatment) in both age groups. The maximal oxygen uptake (VO2max) was measured using a direct incremental ergometer test. In the young subjects, the VO2max after placebo and ubiquinone treatment was 58.5 (95% confidence interval: 53.0-64.0) and 59.0 ml.min-1.kg-1 (52.2-66.8), respectively. The corresponding results in the older subjects were: 37.2 (31.7-42.7) and 33.7 ml.min-1.kg-1 (26.2-41.7) (P < 0.0001 for age group, P > 0.05 for treatment). In a prolonged test (60-min submaximal, then incremental load until exhaustion) time to exhaustion was longer after the placebo [young men: 85.7 (82.4-89.0), older men: 82.9 min (75.8-89.9)] than after ubiquinone [young men: 82.1 (78.5-85.8), older men: 77.2 min (70.1-83.7); P = 0.0003 for treatment]. Neither ubiquinone supplementation nor exercise affected serum malondialdehyde concentration. Oral ubiquinone was ineffective as an ergogenic aid in both the young and older, trained men.
Article
The essential role of coenzyme Q--ubiquinone--in biological energy transduction is well established. Reduced Q--ubiquinol--has also been shown to act as an antioxidant and to decrease the action of free radicals, which in turn could cause damage to structural lipids or proteins. The accumulation of lipopigments during aging in several peripheral organs and in the nervous system is considered to be related to the peroxidation of unsaturated fatty acids. An age-related decline of Q-10 has been suggested to occur in man and rats. In this study we followed the effects of life-long oral supplementation of coenzyme Q-10 on the development and life-span and pigment accumulation in peripheral tissues and the nervous system of laboratory rats. The Q-10 supplemented group showed a significant increase in Q-10 in plasma and liver, while it was unchanged in other tissues. There was no significant difference between the two groups in the development and mortality of the animals. No differences were observed in lipopigment accumulation. Our results indicate that in rats, life-long supplementation of Q-10 has no beneficial effects on life-span or pigment accumulation.
Article
The relationship between, lipid peroxidation induced by ascorbate and adenosine ADP/Fe3+, and its effect on the respiratory chain activities of beef heart submitochondrial particles has been investigated. Lipid peroxidation, measured as thiobarbituric acid reactive substance formation, resulted in an inhibition of the NADH and succinate oxidase activities. Examination of several partial reactions of the respiratory chain revealed inactivation primarily of those involving endogenous ubiquinone, i.e., NADH- and succinate-ubiquinone1 and cytochrome c reductases. Ubiquinol-cytochrome c reductase, measured with reduced ubiquinone2 as electron donor, was unaffected. The amount of NADH- or succinate-reducible cytochrome b in the presence of cyanide was strongly decreased, but could be recovered by the addition of antimycin. There occurred a substantial decrease of the ubiquinone content in the course of lipid peroxidation, with a linear relationship between this decrease and the NADH and succinate oxidase activities. The results are consistent with the conclusion that the ubiquinone pool undergoes an oxidative modification during lipid peroxidation, to a form that can no longer function as a component of the respiratory chain. Lipid peroxidation also led to a partial inhibition of the succinate dehydrogenase and cytochrome c oxidase activities and a minor decrease of the cytochrome c and cytochrome a contents. Reduction of endogenous ubiquinone prevented lipid peroxidation as well as the concomitant modification of ubiquinone and inactivation of the respiratory chain. These observations suggest that the destruction of ubiquinone through lipid peroxidation is the primary cause of inactivation of the respiratory chain, and emphasize the antioxidant role of ubiquinol in preventing these effects. The possible implications of these findings for regulation of the cellular turnover of ubiquinone by the prevailing oxidative stress are discussed.
Article
The effect of lifelong oral supplementation with ubiquinone Q10 (10 mg/kg/day) was examined in Sprague-Dawley rats and C57/B17 mice. There were no significant differences in survival or life-span found in either rats or mice. Histopathologic examination of different rat tissues showed no differences between the groups. In Q10 supplemented rats, plasma and liver Q10 levels were 2.6 to 8.4 times higher at all age points than in control rats. Interestingly, in supplemented rats the Q9 levels also were significantly higher (p<0.05) in plasma and liver at ages 18 and 24 months. Neither Q9 nor Q10 levels were affected by supplementation in kidney, heart, or brain tissues. In spite of the significant changes in plasma and liver ubiquinone concentrations, lifelong Q10 supplementation did not prolong or shorten the lifespan of either rats or mice.
Article
Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, plasma LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q10). Recent studies have shown that in oxidizing plasma lipoproteins alpha-TOH can exhibit anti- or pro-oxidant activities for the lipoprotein's lipids exposed to a vast array of oxidants. This article reviews the molecular action of alpha-TOH in LDL undergoing "mild" radical-initiated lipid peroxidation, and discusses how small levels of CoQ10H2 can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels alpha-TOH, CoQ10H2 and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q10 supplementation on atherogenesis in apolipoprotein E knockout mice.