Biofactors - Volume 32, issue 1-4

Authors: Li, Geng | Jack, Clifford R. | Yang, Xi-Fei | Yang, Edward S.

Article Type: Research Article

Abstract: We tested the hypotheses that supplemental intake of the diet supplement Coenzyme Q_{10} (CoQ_{10} ) could delay brain atrophy in double transgenic amyloid precursor protein (APP) / presenilin 1 (PS1), single transgenic APP and PS1 as well as wild type mice by volume MR image in vivo. One hundred and twelve mice (28 APP/PS1, 28 APP, 28 PS1 and 28 wild types) were studied. Half of each genotype group (n = 14 …per group) was treated with CoQ_{10} 2400 mg/kg/day, and the other half with placebo for 60 days. Magnetic resonance (MR) images were used to obtain the volumes of the hemispheres and hippocampi. APP / PS1, APP, PS1 and wild type mice treated with CoQ_{10} exhibited significantly less atrophy in hemisphere and hippocampus than those receiving placebo. The neuro-protective effect of the CoQ_{10} on hemispheric volume, and hippocampal volume was related to genotype; greater in APP/PS1 than APP and PS1 mice and less in wild type mice. Our result indicated that CoQ_{10} may have therapeutic potential in the prevention and treatment of MCI and AD. Show more

Keywords: APP/PS1 double transgenic mice, antioxidant, Alzheimer's disease, hippocampal volume, hemispheric volume

Citation: BioFactors, vol. 32, no. 1-4, pp. 169-178, 2008

Authors: Schmelzer, Constance | Lindner, Inka | Rimbach, Gerald | Niklowitz, Petra | Menke, Thomas | Döring, Frank

Article Type: Research Article

Abstract: Clinical studies demonstrated the efficacy of Coenzyme Q_{10} (CoQ_{10} ) as an adjuvant therapeutic in cardiovascular diseases, mitochondrial myopathies and neurodegenerative diseases. More recently, expression profiling revealed that Coenzyme Q_{10} (CoQ_{10} ) influences the expression of several hundred genes. To unravel the functional connections of these genes, we performed a text mining approach using the Genomatix BiblioSphere. We identified signalling pathways of G-protein coupled receptors, JAK/STAT, …and Integrin which contain a number of CoQ_{10} sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin, vitronectin receptor, and C-reactive protein are regulated by CoQ_{10} via the transcription factor NFκB1. To test this hypothesis, we studied the effect of CoQ_{10} on the NF$\kappa$B1-dependent pro-inflammatory cytokine TNF-α. As a model, we utilized the murine macrophage cell lines RAW264.7 transfected with human apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of 2.5 μM or 75 μM CoQ_{10} the LPS-induced TNF-α response was significantly reduced to 73.3 ± 2.8% and 74.7 ± 8.9% in apoE3 or apoE4 cells, respectively. Therefore, the in silico analysis as well as the cell culture experiments suggested that CoQ_{10} exerts anti-inflammatory properties via NFκB1-dependent gene expression. Show more

Keywords: Coenzyme Q_{10}, gene expression, in silico analysis, inflammation, TNF-α

Citation: BioFactors, vol. 32, no. 1-4, pp. 179-183, 2008

Authors: Teran, Enrique | Chedraui, Peter | Racines-Orbe, Marcia | Vivero, Sandra | Villena, Francisco | Duchicela, Fabian | Nacevilla, Luis | Schwager, Gino | Calle, Andres

Article Type: Research Article

Abstract: Background: Preeclampsia is a common disorder of pregnancy exhibiting abnormal plasma and placental coenzyme Q_{10} (CoQ_{10} ) levels when compared to normal pregnancies. Objective: To evaluate CoQ_{10} levels both in plasma and placenta among normal pregnant (n = 60) and preeclamptic (n = 63) primigravid women and determine the effect of high or low altitude residency. Study design: CoQ_{10} was determined using High Performance Liquid Chromatography (HPLC) technique and …group comparisons were performed. Results: Preeclamptic women living at high altitude displayed significantly lower CoQ_{10} plasma levels (0.64 ± 0.23 vs. 0.82 ± 0.46 μmol/L, p = 0.05). No differences were found in CoQ_{10} plasma levels among women living at sea level. Interestingly, plasma CoQ_{10} levels at low altitude in normal pregnancies were significantly lower than high altitude normal pregnancies. Compared to normal pregnancies, preeclamptic women displayed higher placental CoQ_{10} content, which was only significant among those living at sea level (0.120 ± 0.07 vs. 0.076 ± 0.04 ng/mg protein, p < 0.005). Normal pregnant women living at high altitude displayed higher placental CoQ_{10} content when compared to those residing at sea level (p < 0.0005). Conclusion: Women suffering from preeclampsia (high or low altitude) display high placental CoQ_{10} content, with significant low plasma CoQ_{10} levels among those residing in high altitude. More research is warranted to establish the cause-effect relationship between CoQ_{10} levels and preeclampsia. Show more

Keywords: Coenzyme Q_{10}, preeclampsia, pregnancy, placenta, altitude

Citation: BioFactors, vol. 32, no. 1-4, pp. 185-190, 2008

Authors: Haas, Dorothea | Niklowitz, Petra | Hoffmann, Georg F. | Andler, Werner | Menke, Thomas

Article Type: Research Article

Abstract: Introduction: SLOS is caused by a defect of cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to improve biochemical parameters in this condition, but they have also been associated with CoQ_{10} deficiency in patients with hypercholesterolemia. The aim of this study was to analyse plasma and intracellular CoQ_{10} levels in SLOS patients and to determine the influence of HMG-CoA reductase inhibitors. Methods: Plasma concentrations of CoQ_{10} and vitamin E …were measured in 14 patients, intracellular CoQ_{10} levels were determined in platelets of 10 patients with SLOS and compared to controls. Results: Plasma CoQ_{10} and vitamin E levels were significantly lower in SLOS patients. This difference equalised after adjustment to cholesterol concentrations. Treatment with simvastatin did not influence CoQ_{10} levels and redox status. Platelet CoQ_{10} concentrations were similar between patients and controls but there were striking differences in the CoQ_{10} redox status with a decrease of oxidised CoQ_{10} . Conclusion: Decreased concentrations of plasma CoQ_{10} and vitamin E in SLOS patients are due to a diminished carrier capacity. The higher percentage of reduced CoQ_{10} in platelets points to an up-regulation of mitochondrial protection mechanisms. Further studies are needed to evaluate a possible benefit of CoQ_{10} supplementation in SLOS patients. Show more

Keywords: Smith-Lemli-Opitz syndrome, cholesterol biosynthesis, Coenzyme Q_{10}, HMG-CoA reductase inhibitors

Citation: BioFactors, vol. 32, no. 1-4, pp. 191-197, 2008

Authors: Hidaka, Takayoshi | Fujii, Kenji | Funahashi, Iwao | Fukutomi, Naoki | Hosoe, Kazunori

Article Type: Research Article

Abstract: Coenzyme Q_{10} (CoQ_{10}) is a naturally occurring component present in living cells. Its physiological function is to act as an essential cofactor for ATP production, and to perform important antioxidant activities in the body. In most countries, CoQ_{10} has been widely used as a dietary supplement for more than 20 years. Recently, the use of CoQ_{10} as a dietary supplement has grown with a corresponding increase in daily …dosage. The present review describes the safety profile of CoQ_{10} on the basis of animal and human data. The published reports concerning safety studies indicate that CoQ_{10} has low toxicity and does not induce serious adverse effects in humans. The acceptable daily intake (ADI) is 12mg/kg/day, calculated from the no-observed-adverse-effect level (NOAEL) of 1200 mg/kg/day derived from a 52-week chronic toxicity study in rats, i.e., 720 mg/day for a person weighing 60 kg. Risk assessment for CoQ_{10} based on various clinical trial data indicates that the observed safety level (OSL) for CoQ_{10} is 1200 mg/day/person. Evidence from pharmacokinetic studies suggest that exogenous CoQ_{10} does not influence the biosynthesis of endogenous CoQ_{9} /CoQ_{10} nor does it accumulate into plasma or tissues after cessation of supplementation. Overall, these data from preclinical and clinical studies indicate that CoQ_{10} is highly safe for use as a dietary supplement. Additionally, analysis of CoQ_{10} bioavailability or its pharmacokinetics provides the pertinent safety evaluation for CoQ_{10} . Show more

Keywords: Coenzyme Q_{10}, CoQ_{10}, ubiquinol, safety profile, dietary supplement, ADI, OSL, CoQ_{10} biosynthesis

Citation: BioFactors, vol. 32, no. 1-4, pp. 199-208, 2008

Authors: Nukui, Kazuki | Yamagishi, Toshihiko | Miyawaki, Hiromi | Kettawan, Aikkarach | Okamoto, Tadashi | Belardinelli, Romualdo | Tiano, Luca | Littarru, Gian Paulo | Sato, Kiyoshi

Article Type: Research Article

Abstract: Coenzyme Q_{10} (CoQ_{10} ) is known to be highly hydrophobic and, as such, insoluble in water: this leads to serious inconvenience when trying to incorporate it in food products. Its absorption is also known to be very limited. PureSorb-Q™40 (P40) (Water-soluble type CoQ_{10} powder, CoQ_{10} content 40 w/w % was developed in order to improve its use with food products and to enhance its absorption. In the …present study the absorption of this novel formulation was compared to a conventional lipid soluble CoQ_{10} by administering both products to rats and humans. Acute, single-administration studies in rats showed that P40 has a higher absorption, compared to lipid soluble CoQ_{10} , both in prandial and fasting states. Similarly, single administration in humans revealed a higher absorption level for P40, taken in the fasting state or together with meals. In the rat study, no adverse effects were observed with P40 at doses up to 2,000 mg/kg in both sexes. In a double-blind, placebo controlled, comparative study conducted on 46 healthy volunteers and randomly divided into two groups, in the group receiving 900~mg of CoQ_{10} per day, for 4 consecutive weeks, the average level at two weeks was 8.79 ± 3.34 μg/mL, similar to the corresponding level after 4 weeks (8.33 ± 4.04 μg/mL). After 2 weeks of washout, serum CoQ_{10} level decreased to 1.30 ± 0.49 μg/mL. P40 intake did not cause any significant changes in symptoms and clinical laboratory tests as assessed by physical, hematological, blood biochemical or urinalysis. Clinical examinations also did not reveal any abnormalities. The above blood (serum) CoQ_{10} level at 2 weeks after start of intake was compared with other reported values. The same dose of CoQ_{10} (900mg/day), when administered by softgel capsules yielded a plasma CoQ_{10} concentration of 3.6 μg/mL, while P40 levels were 8.79 ± 3.34 mug/mL. These levels are remarkably high for instance when compared to the corresponding levels obtained, in patients affected by Parkinson's disease, with CoQ_{10} doses up to 2,400mg/day. A clinical study was conducted using doses of 300 mg/day and 600 mg/day, in patients affected by cardiovascular disease. Also in this case there was linearity in the response with the levels obtained by administering P40 at a dose of 100 and 900 mg/day. Show more

Keywords: Coenzyme Q_{10}, PureSorb-™Q40, P40, absorption, uptake, rat, human, blood CoQ_{10} level

Citation: BioFactors, vol. 32, no. 1-4, pp. 209-219, 2008

Authors: Morré, Dorothy M. | Morré, D. James | Rehmus, Wingfield | Kern, Dale

Article Type: Research Article

Abstract: Our work has identified an aging-related ECTO-NOX activity (arNOX), a hydroquinone oxidase which is cell surface located and generates superoxide. This activity increases with increasing age beginning >30 y. Because of its cell surface location and ability to generate superoxide, the arNOX proteins may serve to propagate an aging cascade both to adjacent cells and to oxidize circulating lipoproteins as significant factors determining atherogenic risk. The generation of superoxide by arNOX proteins is inhibited …by Coenzyme Q_{10} as one basis for an anti-aging benefit of CoQ_{10} supplementation in human subjects. In a preliminary pilot study, 25 female subjects between 45 and 55 y of age were recruited at Stanford University from the Palo Alto, CA area. Informed consent was obtained. Ten of the subjects received Coenzyme Q_{10} supplementation of 180 (3 × 60 mg) per day for 28 days. Serum, saliva and perspiration levels of arNOX were determined at 7, 14 and 28 days of CoQ_{10} supplementation and compared to the initial baseline value. Activity correlated with subject age up to a maximum between age 50 and 55 years of age for saliva and perspiration as well and then declined. With all three sources, the arNOX activity extrapolated to zero at about age 30. Response to Coenzyme Q_{10} also increased with age being least between ages 45 and 50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity was reduced between 25 and 30% by a 3 × 60 mg daily dose Coenzyme Q_{10} supplementation. Inhibition was the result of Coenzyme Q_{10} presence. Show more

Citation: BioFactors, vol. 32, no. 1-4, pp. 221-230, 2008

Authors: Morré, D. James | Morré, Dorothy M.

Article Type: Research Article

Abstract: arNOX is a coenzyme Q_{10} -inhibited, aging-related ECTO-NOX protein of the cell surface also present in sera. It is capable of superoxide generation measured as superoxide dismutase-inhibited reduction of ferricytochrome c and is a potential contributor to atherogenic risk. Here, we report an arNOX activity of saliva of older individuals also inhibited by coenzyme Q_{10} . The activity first appears after age 30 to a near maximum at about age 55. Those surviving beyond …age 55 usually have reduced arNOX activities. Our studies demonstrate significant (25 to 30%) reduction of arNOX levels with coenzyme Q_{10} supplementation of 60 mg (2 × 30 mg) per day for 28 days. Activity correlated with age. Response to coenzyme Q_{10} increased with age being greatest between ages 60 and 65. Saliva arNOX levels varied in a regular pattern throughout the day so it was important that samples be collected at approximately the same time each day for comparative purposes. The coenzyme Q_{10} response was reversible and within 12 h after the last intake of coenzyme Q_{10} , the salivary arNOX levels returned to base line. The findings suggest that salivary arNOX provides a convenient and non-invasive method to monitor arNOX levels in clinical coenzyme Q_{10} intervention trials with the response levels paralleling those seen with serum and cellular arNOX. Show more

Citation: BioFactors, vol. 32, no. 1-4, pp. 231-235, 2008

Authors: Inui, M. | Ooe, M. | Fujii, K. | Matsunaka, H. | Yoshida, M. | Ichihashi, M.

Article Type: Research Article

Abstract: Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species (ROS). ROS are thought to be a major factor to initiate the up-regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation. Coenzyme Q_{10} …(CoQ_{10} ) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA-induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation-induced cytokine production in keratinocytes may be inhibited by CoQ_{10} , resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB-induced IL-6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ_{10} . Furthermore, MMP-1 production of fibroblasts cultured with the medium containing CoQ_{10} collected from UVB-irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ_{10} cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ_{10} may inhibit the production of IL-6 which stimulate fibroblasts in dermis by paracrine manner to up-regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin. Show more

Keywords: UVB, matrix metalloproteinase (MMP), keratinocyte, cytokine, wrinkle

Citation: BioFactors, vol. 32, no. 1-4, pp. 237-243, 2008

Authors: Prahl, S. | Kueper, T. | Biernoth, T. | Wöhrmann, Y. | Münster, A. | Fürstenau, M. | Schmidt, M. | Schulze, C. | Wittern, K.-P. | Wenck, H. | Muhr, G.-M. | Blatt, T.

Article Type: Research Article

Abstract: The functional loss of mitochondria represents an inherent part in modern theories trying to explain the cutaneous aging process. The present study shows significant age-dependent differences in mitochondrial function of keratinocytes isolated from skin biopsies of young and old donors. Our data let us postulate that energy metabolism shifts to a predominantly non-mitochondrial pathway and is therefore functionally anaerobic with advancing age. CoQ_{10} positively influences the age-affected cellular metabolism and …enables to combat signs of aging starting at the cellular level. As a consequence topical application of CoQ10 is beneficial for human skin as it rapidly improves mitochondrial function in skin in vivo. Show more

Keywords: CoQ_{10}, topical application, skin aging, keratinocytes, glucose, lactate, mitochondria

Citation: BioFactors, vol. 32, no. 1-4, pp. 245-255, 2008

Authors: Bompadre, Stefano | Tulipani, Sara | Romandini, Stefania | Giorgetti, Raffaele | Battino, Maurizio

Article Type: Research Article

Abstract: A novel isocratic modified column-switching HPLC method for automated quantitative analysis of Vitamin E and Coenzyme Q, in the reduced and oxidized form, is described. Many column-switching HPLC methods are found in the literature, also for determining antioxidant substances, but we developed a different system of column-switching. An empty column, 5 cm long, was connected to the switching valve, before the sample loop and the extraction column. The sample loop was connected directly after the empty …column. The inserted column, containing about 1.4 ml of the extraction eluent simulated a gradient elution, enhancing sensitivity and resolution. When switching the columns, the empty column is placed right before the extraction column and acts as a static mixer for the extraction phase and the incoming analytical phase. Samples were cleaned from interfering compounds by transfer onto a extraction-column, using a C-8 silica. Separation was performed onto an analytical column C18 3 μm, 150 mm × 4.6 mm at a flow rate of 1.0 ml/min with 20 mmol/l lithium perchlorate/perchloric acid, pH3.0 in Ethanol as analytical eluent. Detection was performed with a ESA Coulochem 5100 A model. The method was found to be suitable for automated analysis of Coenzyme Q, reduced and oxidized form, and Vitamin E in serum. Show more

Keywords: Solid-phase extraction, column-switching, HPLC-EC

Citation: BioFactors, vol. 32, no. 1-4, pp. 257-262, 2008

Authors: Ramirez-Tortosa, M. Carmen | Granados, Sergio | Ramirez-Tortosa, Cesar L. | Ochoa, Julio J. | Camacho, Pedro | García-Valdés, Luz | Battino, Maurizio | Quiles, Jose L.

Article Type: Research Article

Abstract: The effects of the administration of water soluble coenzyme Q_{10} (25 mg/kg per day) over 30 days, after 50 days feeding on a high-fat diet (3% lard + 1.3% cholesterol), were investigated in the plasma and liver mitochondria of rabbits. Results showed that this atherogenic diet enhanced lipid levels both in plasma and liver mitochondria, reduced plasma and mitochondrial concentrations of retinol and coenzyme Q_{10} , led to higher DNA damage in peripheral …blood lymphocytes and reactive oxygen species concentration in liver mitochondria. The treatment of animals with coenzyme Q_{10} reduced (to the healthy group levels) lipid concentration in liver mitochondria with no effect on plasma lipids, increased mitochondrial levels of α-tocopherol, restored mitochondrial coenzyme Q_{10} and improved α-tocopherol levels in plasma. Moreover, coenzyme Q_{10} supplementation reduced mitochondrial reactive oxygen species levels and decreased DNA damage in peripheral blood lymphocytes. The findings suggest that antioxidant therapy with coenzyme Q_{10} may be used in the treatment of liver pathologies associated to the intake of high-fat, atherogenic, diets. Show more

Keywords: Comet assay, dichlorofluorescein, DNA strand breaks, high fat diet, retinol, tocopherol, ubiquinone, vitamin A, vitamin E

Citation: BioFactors, vol. 32, no. 1-4, pp. 263-273, 2008

Article Type: Other

Citation: BioFactors, vol. 32, no. 1-4, pp. 275-275, 2008