Oral Administration Of Coenzyme Q10 Research Articles

The State of Lipid Metabolism in Old Rats in High Altitude Conditions Against the Background of the Use of Coenzyme Q10

The problem of population aging is relevant both in Kyrgyzstan and in the global space. At the same time, the preservation of the functional capabilities of the body of elderly people living in adverse climatic conditions is of particular importance. 20-30% of the inhabitants live in the mountainous area of Kyrgyzstan at an altitude of 2000-4000 meters above sea level. It is known that in high-altitude conditions, the body is influenced by extreme factors of the highlands, which accelerate the aging process and reduce life expectancy. This article presents data from experimental studies of energy metabolism disorders in old rats and its correction of coenzyme Q10 at an altitude of 3200 m above sea level. It was found that in old rats, under conditions of short-term adaptation in the mountains, an increase in the level of total cholesterol, triglycerides and low-density lipoproteins was shown, and the level of high-density lipoproteins decreased, indicating a violation of lipid metabolism. Also, due to oxidative stress in high-altitude conditions, the level of malondialdehyde, superoxide dismutase and catalase in the blood of animals was increased. Oral administration of coenzyme Q10 at a dose of 30 mg/kg of body weight 1 time per day for 30 days to old rats led to a decrease in total cholesterol, low-density lipoproteins, triglycerides and an increase in high-density lipoproteins, due to the fact that coenzyme Q10 protects the plasma membrane of the cell from lipid peroxidation, preventing oxidative modifications lipids, which leads to a reduced risk of coronary heart disease, heart attack and stroke.

Oral administration of coenzyme Q10 ameliorates memory impairment induced by nicotine-ethanol abstinence through restoration of biochemical changes in male rat hippocampal tissues

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.

ALDH2 deficiency induces atrial fibrillation through dysregulated cardiac sodium channel and mitochondrial bioenergetics: A multi-omics analysis

Point mutation in alcohol dehydrogenase 2 (ALDH2), ALDH2*2 results in decreased catalytic enzyme activity and has been found to be associated with different human pathologies. Whether ALDH2*2 would induce cardiac remodeling and increase the attack of atrial fibrillation (AF) remains poorly understood. The present study evaluated the effect of ALDH2*2 mutation on AF susceptibility and unravelled the underlying mechanisms using a multi-omics approach including whole-genome gene expression and proteomics analysis. The in-vivo electrophysiological study showed an increase in the incidence and reduction in the threshold of AF for the mutant mice heterozygous for ALDH2*2 as compared to the wild type littermates. The microarray analysis revealed a reduction in the retinoic acid signals which was accompanied by a downstream reduction in the expression of voltage-gated Na+ channels (SCN5A). The treatment of an antagonist for retinoic acid receptor resulted in a decrease in SCN5A transcript levels. The integrated analysis of the transcriptome and proteome data showed a dysregulation of fatty acid β-oxidation, adenosine triphosphate synthesis via electron transport chain, and activated oxidative responses in the mitochondria. Oral administration of Coenzyme Q10, an essential co-factor known to meliorate mitochondrial oxidative stress and preserve bioenergetics, conferred a protection against AF attack in the mutant ALDH2*2 mice. The multi-omics approach showed the unique pathophysiology mechanisms of concurrent dysregulated SCN5A channel and mitochondrial bioenergetics in AF. This inspired the development of a personalized therapeutic agent, Coenzyme Q10, to protect against AF attack in humans characterized by ALDH2*2 genotype.

Q10 Co-enzyme Effect on Fetus Implantation in ART Cycles

Background and Aim: Infertility is a common condition that affects many couples. Although current cutting-edge therapeutic methods have been found promising in this regard, their success still is not sufficiently high. Accordingly, researchers are working to develop new methods to augment the likelihood of successful results of Assisted Reproductive Technology (ART). Recently, coenzyme Q10 has been recognized an important and influential factor in the process of reproduction and some scarce studies have been along favorable results in this regard. This study aims to examine the effect of oral administration of coenzyme Q10 on embryo implantation in ART cycles. Methods and Materials: In this randomized, placebo-controlled clinical trial, a total of 128 infertile females who were candidates for ART were randomized in two groups receiving either a daily capsule of coenzyme Q10 by the commencement of gonadotropin through to pregnancy test result (case group, 64 patients), or placebo (control group, 64 patients). Finally, oocyte count, fertilization rate, embryo count, quality of embryos, transferred embryo count, implantation rate and pregnancy rate were compared between the two groups. Results: The mean age of the patients was 32.77±6.01 years (20-41) in the case group and 32.45±5.93 years (20-42) in the case group, with no significant difference between the two groups (p=0.77). In comparison between the case and control groups, in spite of better results in the case group, no significant difference was found in terms of oocyte count (10.47±7.16 and 9.38±7.52, respectively; p=0.40), fertilization rate (66.88±16.08 % and 66.73±21.50 %, respectively; p=0.96), embryo count (7.03±4.78 and 5.84±4.85, respectively; p=0.17), quality of embryos (71.9% grade I and 28.1% grade II in cases, 68.8% grade I and 31.3% grade II in controls; p=0.70) transferred embryo count (10.9% one, 56.3% two-three and 32.8% more than three in cases, 14% one, 56.3% two-three and 29.7% more than three in controls; p=0.84), implantation rate (8.39±12.73 % and 7.22±12.80 %, respectively; p=0.60), and pregnancy rate (34.4% and 26.6%, respectively; p=0.34). Conclusion: Although using coenzyme Q10, in comparison with placebo, was along with better results in terms of outcome variables of ART, the difference was statistically insignificant possibly because of a small sample size and short duration of the intervention.

Oral administration of Coenzyme Q10 protects mice against oxidative stress and neuro-inflammation during experimental cerebral malaria

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 Q10 (CoQ10) 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 CoQ10 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 CoQ10 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 CoQ10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ10 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.

CoQ10 ameliorates mitochondrial dysfunction in diabetic nephropathy through mitophagy.

The molecular signaling mechanisms of Coenzyme Q10 (CoQ10) in diabetic nephropathy (DN) remain poorly understood. We verified that mitochondrial abnormalities, like defective mitophagy, the generation of mitochondrial reactive oxygen species (mtROS) and the reduction of mitochondrial membrane potential, occurred in the glomerulus of db/db mice, accompanied by reduced PINK and parkin expression and increased apoptosis. These changes were partially reversed following oral administration of CoQ10. In inner fenestrated murine glomerular endothelial cells (mGECs), high glucose (HG) also resulted in deficient mitophagy, mitochondrial dysfunction and apoptosis, which were reversed by CoQ10. Mitophagy suppression mediated by Mdivi-1 or siPINK abrogated the renoprotective effects exerted by CoQ10, suggesting a beneficial role for CoQ10-restored mitophagy in DN. Mechanistically, CoQ10 restored the expression, activity and nuclear translocation of Nrf2 in HG-cultured mGECs. In addition, the reduced PINK and parkin expression observed in HG-cultured mGECs were partially elevated by CoQ10. CoQ10-mediated renoprotective effects were abrogated by the Nrf2 inhibitor ML385. When ML385 abolished mitophagy and the renoprotective effects exerted by CoQ10, mGECs could be rescued by treatment with mitoTEMPO, which is a mtROS-targeted antioxidant. These results suggest that CoQ10, as an effective antioxidant in mitochondria, exerts beneficial effects in DN via mitophagy by restoring Nrf2/ARE signaling.

Coenzyme Q10 Protect Mice Against Inflammatory Responses During Experimental Cerebral Malaria

Malaria is a life threatening infectious diseases transmitted by the bite of infected female Anopheles mosquito and responsible for high morbidity and mortality rates. Cerebral malaria is a complex neurological syndrome, whose pathology is mediated by inflammatory processes triggered by the immune system of the host following infection with Plasmodium falciparum. Coenzyme Q10 is an obligatory cofactor in the electron transport chain. The reduced form of Coenzyme Q10 serves as a potent antioxidant additionally; Coenzyme Q10 has been identified as a modulator of gene expression, inflammation and apoptosis. However, the modulatory effects of Coenzyme Q10 Plasmodium berghei ANKA infection process and risk occurrence of experimental cerebral malaria (ECM) have not been determined. The aim of this study was to elucidate the putative impact of oral administration of Coenzyme-Q10 on the initiation or regulation of inflammatory immune response in ECM of C57BL/6 mice during Plasmodium berghei ANKA (PbA) infection. We observed that oral administration of Coenzyme-Q10 both before and after PbA infection significantly hampered infiltration of inflammatory monocytes into the brain. Furthermore, pro-inflammatory cytokine TNF-α, which is associated with inflammation during ECM, was down-regulated in Coenzyme-Q10 administered mice. Remarkably, Coenzyme-Q10 was very effective in inhibiting dendritic cell differentiation. These data collectively demonstrated the immuno-modulatory function of Coenzyme-Q10 on host inflammatory responses during ECM. Keywords: Plasmodium berghei ANKA, Coenzyme Q10, experimental cerebral malaria DOI : 10.7176/JNSR/9-2-05

The Plasma Bioavailability of Coenzyme Q10 Absorbed from the Gut and the Oral Mucosa.

Coenzyme Q10 (CoQ10) has a central role in the generation of cellular bioenergy and its regulation. The hydrophobicity exhibited by the CoQ10 molecule leads to reports of poor absorption profiles, therefore, the optimization of formulations and modes of delivery is an ever-evolving therapeutic goal. The aim of this study was to investigate different CoQ10 formulations. The article summarizes the findings from an Australian comparative study involving adults administered CoQ10 through different oral delivery platforms. A total of 11 participants (six males and five females) voluntarily participated in a comparative clinical study of three different CoQ10 formulations across a six-week period, completing 198 person-hours of cumulative contribution equivalent to n = 33 participation. All of the eligible participants (n = 11) administered the three formulations blinded from who the commercial supplier of the formulation was and from what the chemical form of the CoQ10 was that was being administered. The dosing between the CoQ10 preparations were dispensed sequentially and were administered following three-week washouts. Three commercial preparations were tested, which included the following: formulations with capsules each containing ubiquinol and ubiquinone (150 mg/capsule), and a liposome ubiquinone formulation (40 mg/mL at 2 actuations of the pump). A significant inter-subject variation in the plasma level of CoQ10 at baseline that was observed to increase with an increase in age. This trend persisted in the post administration of the different formulations. Furthermore, it was observed that the intestinal absorption and bioavailability of CoQ10 varied significantly in the plasma between subjects, irrespective of whether the ubiquinol or ubiquinone forms were administered. The administration of CoQ10 as a liposome for preparation showed the poorest response in bioavailability. Although the ubiquinol capsule form of CoQ10 was observed to have increased in the plasma versus the ubiquinone capsules and the ubiquinol liposome at the two-hour interval, the inter-subject variation was such that the difference was not significant (p > 0.05). All of the CoQ10 formulations showed no further increases in their plasma levels over the remaining study period (i.e., four hours). This study further concluded that the intestinal absorption of CoQ10 is highly variable and is independent of the molecular form administered. Furthermore, it also concludes that liposomes are not an effective vehicle for the oral administration of CoQ10, and as such, did not improve the oral mucosal/sublingual absorption and bioavailability of the molecule. Of interest was the observation that with the increasing subject age, there was an observed increase in the baseline plasma CoQ10 levels in the participants prior to dosing. It was posited that the increase in the baseline plasma levels of CoQ10 with an increase in age could be due to the loss of skeletal muscle mass, a result that still needs to be verified.

Bypassing human CoQ10 deficiency

Primary disorders of the human coenzyme Q10 (CoQ10) biosynthesis pathway are a known cause of severe pediatric diseases. So far, oral administration of CoQ10 is the only treatment strategy for affected individuals. However, the real benefit of CoQ10 supplementation remains questionable and clinical studies regarding efficiency are lacking. Here we provide an outlook on novel treatment approaches using CoQ precursor compounds. These metabolic bypass strategies might be a promising alternative for oral CoQ10 supplementation regimens.

コエンザイムQ10摂取が高齢女性の皮膚ガス中の加齢臭成分ノネナールに与える影響

コエンザイムQ10摂取が高齢女性の皮膚ガス中の加齢臭成分ノネナールに与える影響

The effects of coenzyme Q10 on seizures in mice: The involvement of nitric oxide

Coenzyme Q10 is a potent antioxidant in both mitochondria and lipid membranes. It has also been recognized to have an effect on gene expression. This study was designed to investigate whether acute or subchronic treatment with coenzyme Q10 altered the seizures induced by pentylenetetrazole or electroshock in mice. We also evaluated the involvement of nitric oxide in the effects of coenzyme Q10 in pentylenetetrazole-induced seizure models. Acute oral treatment with different doses of coenzyme Q10 did not affect the seizure in intraperitoneal pentylenetetrazole, intravenous pentylenetetrazole, and electroshock models in mice. Subchronic oral administration of coenzyme Q10 (100mg/kg or more) increased time latencies to the onset of myoclonic jerks and clonic seizures induced by intraperitoneal pentylenetetrazole and at the doses of 25mg/kg or more increased the seizure threshold induced by intravenous infusion of pentylenetetrazole. Subchronic doses of coenzyme Q10 (50mg/kg or more) also decreased the incidence of tonic seizures in the electroshock-induced seizure model. Moreover, acute treatment with the precursor of nitric oxide synthesis, l-arginine (60mg/kg), led to a significant potentiation of the antiseizure effects of subchronic administration of coenzyme Q10 (400mg/kg in intraperitoneal and 6.25mg/kg in intravenous pentylenetetrazole tests). Acute treatment with l-NAME (5mg/kg), a nonspecific nitric oxide synthase inhibitor, significantly attenuated the antiseizure effects of subchronic doses of coenzyme Q10 in both seizure models induced by pentylenetetrazole. On the other hand, acute administration of aminoguanidine (100mg/kg), a specific inducible nitric oxide synthase inhibitor, did not affect the seizures in mice treated with subchronic doses of coenzyme Q10 in both intraperitoneal and intravenous pentylenetetrazole tests. In conclusion, only subchronic and not acute administration of coenzyme Q10 attenuated seizures induced by pentylenetetrazole or electroshock. We also demonstrated, for the first time, the interaction between nitric oxide and coenzyme Q10 in antiseizure activity probably through the induction of constitutive nitric oxide synthase.

Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis by Regulating Nitric Oxide and Inflammatory Cytokines

ObjectiveTo investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).Materials and MethodsOA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.ResultsTreatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.ConclusionCoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.

Oral administration of coenzyme Q10 reduces MPTP-induced loss of dopaminergic nerve terminals in the striatum in mice

The neuroprotective effect of coenzyme Q(10) (CoQ(10)) has been reported in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. In this study, we investigated whether oral administration of CoQ(10) could protect the striatal dopaminergic (DAergic) nerve terminals against MPTP-induced toxicity in C57BL/6N mice using immunoisolation technique for DAergic synaptosomes. CoQ(10) significantly attenuated decrease in dopamine transporter as well as in synaptophysin and actin protein levels in DAergic synaptosomes from MPTP-treated mice. The effect of CoQ(10) was also observed in crude synaptosomes fraction, but not in homogenate. Our results indicate that the nerve terminals are a site for the action of CoQ(10) against the MPTP-induced DAergic neurodegeneration.

Coenzyme Q10 Reduces β-Amyloid Plaque in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease

We previously reported that coenzyme Q10 (CoQ10) could reduce intracellular deposition in an aged transgenic mouse model. Here, we further tested the effect of CoQ10 on amyloid plaque in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease (AD). By using immunohistochemistry and magnetic resonance imaging to determine the burden of amyloid plaque, we found that oral administration of CoQ10 can efficiently reduce the burden of the plaques in this mouse model. These data demonstrate that in addition to reducing intracellular deposition of Abeta, CoQ10 can also reduce plaque pathology. Our study further supports the use of CoQ10 as a therapeutic candidate for AD.

Oral administration of coenzyme Q10 prevents cytochrome c release from mitochondria induced by 1-methyl-4-phenylpyridinium ion in mouse brain synaptosomes

Coenzyme Q10 (CoQ10) exerts neuroprotective effects in several in vivo and in vitro models of neurodegenerative disorders. However, the mechanisms of action are not fully understood. The aim in this study was to investigate whether oral administration of CoQ10 could inhibit cytochrome c (cyt c) release from mitochondria induced by 1-methyl-4-phenylpyridinium ion (MPP+), which causes dopaminergic cell death by selective inhibition of complex I of the electron transport chain, in mouse brain synaptosomes. An increase of cyt c was detected in the cytosolic fraction from mouse brain synaptosomes treated with MPP+. Oral administration of CoQ10 prevented the mitochondrial cyt c release in the MPP+-treated synaptosomes. In addition, CoQ10 did not affect the MPP+-induced decrease in mitochondrial oxidation–reduction activity and membrane potential in brain synaptosomes. Our findings demonstrate that MPP+-induced mitochondrial cyt c release in brain synaptosomes is prevented by oral administration of CoQ10 independently of mitochondrial dysfunction prior to the cyt c release.

Antifatigue effects of coenzyme Q10 during physical fatigue

Objective This study examined the effects of coenzyme Q10 administration on physical fatigue. Methods In a double-blinded, placebo-controlled, three crossover design, 17 healthy volunteers were randomized to oral coenzyme Q10 (100 or 300 mg/d) or placebo administration for 8 d. As a fatigue-inducing physical task, subjects performed workload trials on a bicycle ergometer at fixed workloads twice for 2 h and then rested for 4 h. During the physical tasks, subjects performed non-workload trials with maximum velocity for 10 s at 30 min (30-min trial) after the start of physical tasks and 30 min before the end of the tasks (210-min trial). Results The change in maximum velocity from the 30- to the 210-min trial in the 300-mg coenzyme Q10–administered group was higher than that in the placebo group. In addition, subjective fatigue sensation measured on a visual analog scale in the 300-mg coenzyme Q10–administered group after the fatigue-inducing physical task and recovery period was alleviated when compared with that in the placebo group. Conclusion Oral administration of coenzyme Q10 improved subjective fatigue sensation and physical performance during fatigue-inducing workload trials and might prevent unfavorable conditions as a result of physical fatigue.

Effect of coenzyme Q10 on endotoxin induced hepatocyte injury modulation of endotoxin-activated polymorphonuclear neutrophils

The effect of coenzyme Q10 (CoQ10) on hepatocyte injury during endotoxin (ET) shock in rats was studied with special reference to the role of polymorphonuclear neutrophils (PMN). ET shock was induced by intravenous administration of 5 mg/kg ET, and CoQ10 was given at 20 mg/kg once or 3 times orally or intravenously. We examined plasma glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and glutamate dehydrogenase (GLDH) levels, superoxide production by PMN, the phagocytic activity of PMN, the cytotoxicity of PMN to liver cells, and histological changes in the liver. The CoQ10-treated rats showed lower levels of GOT, GPT, and GLDH than rats treated with ET only. When compared to the group given ET only superoxide production by PMN induced by 2-methyl-6-phenyl-3,7-dihydroimidazol [1,2-alpha]pyrazin-3-one (MCLA) was significantly inhibited in the group given CoQ10 intravenously and 3 times orally, but there was no significant difference in the group given CoQ10 once orally. However, the level of superoxide production by PMN stimulated by phorbol myristate acetate (PMA) was lower in all CoQ10-treated rats than in those given ET only. There was no difference in either peripheral PMN counts or PMN phagocytes between the CoQ10-treated group and the group given ET only. Histologically, the hepatocyte injury in all groups that received CoQ10 was milder than that in the ET-only group. No hepatocyte cytotoxicity by PMN was observed in any group that received CoQ10. These results suggest that both intravenous and oral administration of CoQ10 can modulate the endotoxin-activated PMN, and is useful for preventing hepatocyte injury during ET shock.