Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells.

Oxidative damage in endothelial cells is proposed to play an important role in endothelial dysfunction and atherogenesis. We previously reported that the reduced form of coenzyme Q10 (CoQH) effectively inhibits oxidative stress and decelerates senescence in senescence-accelerated mice. Here, we treated human umbilical vein endothelial cells (HUVECs) with HO and investigated the protective effect of CoQH against senescence, oxidative damage, and reduction in cellular functions.

Effects of Pediococcus acidilactici R037 on Serum Triglyceride Levels in Mice and Rats after Oral Administration.

The biological effects of heat-killed Pediococcus acidilactici R037 (R037) were evaluated when orally administered in mice and rats. Oral R037 administration at a daily dose of 10 and 100 mg/kg for 3 wk dose-dependently reduced fasting and non-fasting serum triglyceride concentrations in KK-A/TaJcl mice, a model of type II diabetes, obesity, hypercholesterolemia, and hypertriglyceridemia. Serum levels of free fatty acids in the 100 mg/kg group tended to decrease (not statistically significant), and total cholesterol levels remained unchanged.

Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition.

Our recent studies revealed that supplementation with the reduced form of coenzyme Q10 (CoQH) inhibits oxidative stress and slows the process of aging in senescence-accelerated mice. CoQH inhibits adipocyte differentiation and regulates lipid metabolism. In the present study, we show that dietary supplementation with CoQH significantly reduced white adipose tissue content and improved the function of brown adipose tissue by regulating expression of lipid metabolism-related factors in KKAy mice, a model of obesity and type 2 diabetes.

Enhancement of Fat Oxidation by Licorice Flavonoid Oil in Healthy Humans during Light Exercise.

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recent studies reported that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the livers of mice and rats, while it reduced body weight in overweight human subjects by reducing total body fat. However, the direct effects of LFO on energy metabolism have not been studied in human subjects.

Stability of ubiquinol-10 (reduced form of coenzyme Q10 ) in human blood.

The ratio of ubiquinol-10 in total coenzyme Q10 (TQ10 ) in human plasma has been proposed as a useful biomarker of oxidative stress. Since ubiquinol-10 is easily oxidized in air, it is necessary to perform suitable processing at medical institutions prior to analysis. To establish stable storage conditions for blood to determine the ubiquinol-10/TQ10 ratios properly, the effects of temperature conditions on the stability of ubiquinol-10 were studied.

Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice.

Aim: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice.

Results: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio.

Ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changes in methylation of CpG promoter islands in the liver of mice.

Coenzyme Q(10) is an essential cofactor in the respiratory chain and serves as a potent antioxidant in biological membranes. Recent studies in vitro and in vivo provide evidence that Coenzyme Q(10) is involved in inflammatory processes and lipid metabolism via gene expression. To study these effects at the epigenomic level, C57BL6J mice were supplemented for one week with reduced Coenzyme Q(10) (ubiquinol).

Oral repeated-dose toxicity studies of coenzyme Q10 in beagle dogs.

To support phase III testing of coenzyme Q10 (CoQ₁₀) in humans, we conducted pharmacokinetic and toxicology studies in beagle dogs. Following single gavage administration of CoQ₁₀ at 600, 1200, 1800, or 2400 mg/kg per d no obvious dose response was observed in maximum concentration (C(max)) or area under the curve (AUC) versus time curve at the 3 highest dosages. In a repeated-dose study of CoQ₁₀ at 600, 1200, 1800, or 2400 mg/kg per d for 4 weeks, CoQ₁₀ reached steady state in plasma by 2 weeks at all dosages.

Inhibition by licorice flavonoid oil of glutathione S-transferase-positive foci in the medium-term rat hepatocarcinogenesis bioassay.

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recently, it was reported that licorice and its derivatives have anticarcinogenic activity in some types of tumors. However, the anticarcinogenic activity has not been identified in the liver, which is a major target organ for carcinogenesis in human.

Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a peroxisome proliferator-activated receptor-alpha gene expression signature in SAMP1 mice.

Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (Q(10)H(2), 500 mg/kg BW/day) of coenzyme Q(10) (CoQ(10)). To unravel molecular mechanisms of these CoQ(10) effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (Q(10)H(2)) or oxidized form of CoQ(10) (Q(10)) was performed. Liver seems to be the main target tissue of CoQ(10) intervention, followed by kidney, heart and brain.

Effects of ubiquinol-10 on microRNA-146a expression in vitro and in vivo.

MicroRNAs (miRs) are involved in key biological processes via suppression of gene expression at posttranscriptional levels. According to their superior functions, subtle modulation of miR expression by certain compounds or nutrients is desirable under particular conditions. Bacterial lipopolysaccharide (LPS) induces a reactive oxygen species-/NF-kappaB-dependent pathway which increases the expression of the anti-inflammatory miR-146a.

Safety assessment of coenzyme Q10 (CoQ10).

Coenzyme Q10 (CoQ10) 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, CoQ10 has been widely used as a dietary supplement for more than 20 years.

Subchronic oral toxicity of ubiquinol in rats and dogs.

Ubiquinol is the two-electron reduction product of ubiquinone (coenzyme Q(10) or CoQ(10)) and functions as an antioxidant in both mitochondria and lipid membranes. In humans and most mammals, including dogs, the predominant form of coenzyme Q is coenzyme Q(10), whereas the primary form in rodents is coenzyme Q(9) (CoQ(9)). Therefore, the subchronic toxicity of ubiquinol was evaluated and compared in Sprague-Dawley rats and beagle dogs.

Evaluation of the mutagenic and genotoxic potential of ubiquinol.

Ubiquinol (the reduced form of coenzyme Q(10)) is the two-electron reduction product of ubiquinone (the oxidized form of coenzyme Q(10)), and has been shown to be an integral part of living cells, where it functions as an antioxidant in both mitochondria and lipid membranes. To provide information to enable a Generally Regarded as Safe (GRAS) evaluation for the use of ubiquinol in selected foods, a series of Organisation of Economic Cooperation and Development (OECD) and good laboratory practice (GLP) toxicological studies was conducted to evaluate the mutagenic and genotoxic potential of Kaneka QH brand of ubiquinol. Ubiquinol did not induce reverse mutations in Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA at concentrations up to 5000 mu g/plate, in either the absence and presence of exogenous metabolic activation by rat liver S9.

Absorption of dietary licorice isoflavan glabridin to blood circulation in rats.

Bioavailability of glabridin was elucidated to show that this compound is one of the active components in the traditional medicine licorice. Using a model of intestinal absorption, Caco-2 cell monolayer, incorporation of glabridin was examined. Glabridin was easily incorporated into the cells and released to the basolateral side at a permeability coefficient of 1.

Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and 4-week multiple oral administration to healthy volunteers.

The safety and bioavailability of ubiquinol (the reduced form of coenzyme Q(10)), a naturally occurring lipid-soluble nutrient, were evaluated for the first time in single-blind, placebo-controlled studies with healthy subjects after administration of a single oral dose of 150 or 300 mg and after oral administration of 90, 150, or 300 mg for 4 weeks. No clinically relevant changes in results of standard laboratory tests, physical examination, vital signs, or ECG induced by ubiquinol were observed in any dosage groups. The C(max) and AUC(0-48 h) derived from the mean plasma ubiquinol concentration-time curves increased non-linearly with dose from 1.

Possible tumor development from double positive foci for TGF-alpha and GST-P observed in early stages on rat hepatocarcinogenesis.

Expression of TGF-alpha during promotion of neoplastic development from GST-P-positive foci in rat chemical hepatocarcinogenesis was investigated. One-hundred male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg bodyweight) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0 or 500 p.

Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We determined whether supplementation with coenzyme Q10 (CoQ10) could decelerate aging in SAMP1 mice and its potential role in aging. Plasma concentrations of CoQ10 and CoQ9 decreased with age in SAMP1 but not in SAMR1 mice.

Intra- and interlaboratory calibration of the DR CALUX bioassay for the analysis of dioxins and dioxin-like chemicals in sediments.

In the Fourth National Policy Document on Water Management in The Netherlands, it is defined that in 2003, in addition to the assessment of chemical substances, special guidelines for the assessment of dredged material should be recorded. The assessment of dredged material is based on integrated chemical and biological effect measurements. Among others, the DR CALUX (dioxin responsive-chemically activated luciferase expression) bioassay has tentatively been recommended for inclusion in the dredged material assessment.

Brominated dioxin-like compounds: in vitro assessment in comparison to classical dioxin-like compounds and other polyaromatic compounds.

Recently, several countries agreed to adopt the Stockholm convention on persistent organic pollutants (POPs). One future obligation will be to add other POPs as new evidence becomes available. In vitro cell-based bioassays offer a rapid, sensitive, and relatively inexpensive solution to screen possible POP candidates.

Low-temperature thermal decomposition of dioxin-like compounds in fly ash: combination of chemical analysis with in vitro bioassays (EROD and DR-CALUX).

To investigate the dechlorination of fly ash during low-temperature treatment under oxygen-deficient conditions (thermocatalyic treatment or Hagenmaier process), six fly ash samples from six different incineration plants were treated in a laboratory experiment or in the actual plant, either under ideal (400 degrees C, 120 min) or intermediate (300 degrees C, 30 min) conditions. The aim of the present study was to confirm the decrease in the I-TEQ (international toxicity equivalency) of polychlorinated dibenzo-p-dioxins/-furans (PCDD/Fs) and coplanar polychlorinated biphenyls (co-PXBs) and, also for the first time, the decrease in the sum of dioxin-like toxicity (bioassay- or bio-TEQ) of all kinds of other dioxin-like Ah receptor agonists (such as PXDD/Fs, PXBs, PXN, X = Br, F) measured by two state-of-the-art cell-based Ah receptor-dependent bioassays: H4IIE-Ethoxy-Resorufin-o-Deethylase (EROD) and H4IIE-luc/DR-Chemical Activated Luciferase expression (DR-CALUX). The treatment efficiency was calculated on the basis of the reduction in the I-TEQ and bio-TED values.

Melting and incineration plants of municipal waste. Chemical and biochemical diagnosis of thermal processing samples (emission, residues).

Control of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in emissions and thermal residues from incinerators has been a cause of public concern for more than one decade. Recently, several studies showed that other persistent organic pollutants (POPs) such as coplanar polychlorinated biphenyls (co-PCBs) also have dioxin-like activity and are released from incinerators. Therefore, the present study was aimed at making a risk assessment about dioxin-like activity in extracts of thermal waste residues (e.

Screening of dioxin-like toxicity equivalents for various matrices with wildtype and recombinant rat hepatoma H4IIE cells.

Determination of dioxin-like compounds utilizing in vitro bioassays such as ethoxyresorufin-O-deethylase (EROD) or chemical-activated luciferase expression (DR-CALUX) is an important tool to evaluate their Ah receptor-mediated toxic effects. The aim of this study is to describe advantages and limitations of these bioassays using rat hepatoma (H4IIE) wildtype and recombinant H4IIE cells in a 96 well microtiter plate format. We are using these bioassays for the evaluation of relative responses (REP) from several congeners of dioxins (e.