Coenzyme Q10

Abstract

Folk medical practices of the Pennsylvania Dutch can be broadly classified into three areas: non-occult folk medicine, faith healing, and witchcraft. This eclectic collection addresses the first two areas of practice, focusing primarily on powwowing as it relates to spiritual faith healing and folk cures.     

Inulin attenuates atherosclerosis in apolipoprotein E-deficient mice

Effects of different inulin-type fructan fractions were studied on atherosclerotic plaque formation in male apo E-deficient mice. Thirty-two mice were randomly divided into four groups and received either a semi-purified sucrose-based diet (control group), or diets in which sucrose was replaced in part by various inulin-type fructans (10 g/100 g): long-chain inulin, oligofructose, or an oligofructose-enriched inulin for 16 weeks. The presence of atherosclerotic plaques was assessed by histomorphometry in the aortic sinus. The apo E-deficient mice fed long-chain inulin or an oligofructose-enriched inulin had about 35 % and 25 % less atherosclerotic lesion area compared with the control group, respectively. Feeding long-chain inulin significantly reduced plasma cholesterol concentrations (P<0.001), and the three inulin-type fructans reduced triacylglycerol (TAG) concentrations compared with the control group (P<0.001). Both the long-chain inulin and an oligofructose-enriched inulin significantly lowered hepatic cholesterol concentrations compared with the control diet (P<0.05). Hepatic TAG concentrations were significantly lower in all three groups fed the fructan-supplemented diets v. the control group (P<0.0001). The results of the present study suggest that inhibition of atherosclerotic plaque formation is more potent in the presence of long-chain inulin, either alone or in combination with oligofructose (an oligofructose-enriched inulin), and that this probably is related to changes in lipid metabolism.     

甜菜碱对载脂蛋白E基因缺陷小鼠抗动脉粥样硬化的作用

目的 研究甜菜碱对载脂蛋白E(ApoE)基因缺陷小鼠动脉粥样硬化斑块形成的影响并对其抗炎机制进行初步探讨.方法 7周龄ApoE基因缺陷小鼠(品系C57BL/6J)按体重随机分为4组:模型组和3个甜菜碱组,同龄同品系野生型小鼠作为正常对照组.各组均喂饲AIN-93G基础饲料.3个甜菜碱组分别加入1%、2%、4%甜菜碱.于0、7、14周时测定血清肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1、血脂水平以及主动脉TNF-α基因启动子的甲基化状况;于14周时测定主动脉窦脂质斑块占管腔面积百分比.结果 2%、4%甜菜碱组主动脉窦斑块面积占管腔总面积百分比分别为(11.43±2.65)%和(12.09 ±3.07)%,与模犁组(19.31±5.42)%相比差异有统计学意义(t值分别为3.117和3.010,P值均小于0.01);3个甜菜碱组血清TNF-α分别为(56.33±3.86)、(63.04±4.67)、(65.52±3.97)pg/ml,均明显低于模型组(79.40 ±4.68)pg/ml(t值分别为9.270、6.571、5.576,P值均小于0.001).结论 甜菜碱口J能通过抗炎作用而抑制ApoE基因缺陷小鼠动脉粥样硬化斑块的形成.     

Coenzyme Q10 in health and disease

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.     

Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and in vivo

The key pathogenetic event of many retinopathies is apoptosis of retinal cells. Our previous studies have demonstrated that Coenzyme Q10 (CoQ10) prevents apoptosis of corneal keratocytes both in vitro and in vivo, by virtue of its ability to inhibit mitochondrial depolarization, independently of its free radical scavenger role. The aim of this study was to evaluate whether CoQ10 can protect cultured retinal cells and the retinas of rats from radiation-induced apoptosis, if instilled as eye drops in the cornea. In vitro experiments were carried out on cultured ARPE-19 or RGC-5 cells pretreated with CoQ10 before eliciting apoptosis by UV- and γ-radiation, chemical hypoxia (Antimycin A) and serum starvation. Cell viability was evaluated by light microscopy and fluorescence activated cell sorting analysis. Apoptotic events were scored by time-lapse videomicroscopy. Mitochondrial permeability transition was evaluated by JC-1. The anti-apoptotic effectiveness of CoQ10 in retina was also evaluated by an in situ end-labeling assay in Wistar albino rats treated with CoQ10 eye drops prior to UV irradiation of the eye. CoQ10 substantially increased cell viability and lowered retinal cell apoptosis in response both to UV- and γ-radiation and to chemical hypoxia or serum starvation by inhibiting mitochondrion depolarization. In the rat, CoQ10, even when applied as eye drops on the cornea, protected all retina layers from UVR-induced apoptosis. The ability of CoQ10 to protect retinal cells from radiation-induced apoptosis following its instillation on the cornea suggests the possibility for CoQ10 eye drops to become a future therapeutic countermeasure for radiation-induced retinal lesions.     

Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice

Background  Betaine serves as a methyl donor in a reaction converting homocysteine to methionine. It is commonly used for the treatment of hyperhomocysteinemia in humans, which indicates it may be associated with reduced risk of atherosclerosis. However, there have been few data regarding its vascular effect. Aim of the study  To investigate the effect of betaine supplementation on atherosclerotic lesion in apolipoprotein (apo) E-deficient mice. Methods  Four groups of apoE-deficient mice were fed AIN-93G diets supplemented with 0, 1, 2, or 4 g betaine/100 g diet (no, 1, 2, and 4% betaine, respectively). Wild-type C57BL/6 J mice were fed AIN-93G diet (wild-type). Mice were sacrificed after 0, 7, or 14 weeks of the experimental diets. Atherosclerotic lesion area in the aortic sinus, levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in aorta and serum, serum lipids, and methylation status of TNF-α promoter in aorta were determined. Results  Linear regression analysis showed that the higher dose of betaine was related to smaller atherosclerotic lesion area (β = −11.834, P < 0.001). Compared with no-betaine mice after 14 weeks, mice receiving 1%, 2%, or 4% betaine had 10.8, 41, and 37% smaller lesion area, respectively. Betaine supplementation also reduced aortic expression of TNF-α in a dose-dependent way in four groups of apoE-deficient mice, and Pearson correlation revealed that atherosclerotic lesion area was positively associated with aortic TNF-α level (r = 0.777, P < 0.001). Although serum TNF-α levels were lower in betaine-supplemented mice than in no-betaine mice after fourteen weeks of treatment (P < 0.001), we did not observe a significant dosage effect (P = 0.11). However, methylation level of TNF-α promoter did not differ among groups at any time. In this study, apoE-deficient mice receiving betaine supplementation for 14 weeks had higher concentrations of serum total cholesterol (P < 0.01), LDL cholesterol (P < 0.05), and lower body weight (P < 0.05) than no-betaine mice. Conclusions  These data suggest that despite exacerbating hyperlipidemia in apoE-deficient mice, betaine may exert its anti-atherogenic effect by inhibiting aortic inflammatory response mediated by TNF-α.     

Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice

Background

Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice.

Methods

Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13) and age-matched C57BL/6 control mice (C57, n = 15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two-way ANOVA followed by Fisher's post hoc test was used.

Results

Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 ± 28 vs 358 ± 92 μL/min, p < 0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 ± 1.3 vs 7 ± 0.9 mmol/L, p < 0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 ± 0.6 vs 30 ± 0.9%, respectively, p < 0.05), which was aggravated at 8-month old animals (40 ± 3 and 35 ± 3%, respectively). Tubulointersticial fibrosis was augmented at both young (17 ± 2%, p < 0.05) and adult (20 ± 1%, p < 0.05) ApoE mice compared to respective C57 age controls (8 ± 1 and 12 ± 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains.

Conclusions

These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.

     

Coenzyme Q10 Supplementation and Heart Failure

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Oxida-tive stress appears to play a pivotal role in atherosclerosis. Coenzyme Q10 (CoQ10), one of the most important antioxidants, is synthesized de novo by every cell in the body. Its biosynthesis decreases with age and its deficit in tissues is associated with degenerative changes of aging, thus implicating a possible therapeutic role of CoQ10 in human diseases. There is evidence to support the therapeutic value of CoQ10 as an adjunct to standard medical therapy in congestive heart failure. However, much further research is required, especially in the use of state-of-the-art techniques to assess functional outcomes in patients with congestive heart failure.     

Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice

Background

The effect of an herbal formulation LI85008F on weight loss in obese human subjects was evaluated in an 8-weeks randomized, double-blind, placebo-controlled study (Clinical Trial Registration no. ISRCTN37381706). Fifty obese subjects (Body mass index 30 to 40?kg/m2, 29.3% male; 70.7% female; ages 27?C50?years) were randomized into two groups; placebo (n?=?25) and LI85008F formulation (n?=?25). The participants received either 900?mg/day of LI85008F formulation in three divided doses or three identical placebo capsules and all of them remained on a calorie-controlled diet (2000 cal/day) and 30?min walking for 5?days a week during the entire duration of the study.

Results and discussion

At the end of the trial period, LI85008F supplemented group showed significant net reductions in body weight and Body Mass Index (BMI). The participants who received the herbal formulation, showed reduced fasting blood glucose, LDL, LDL/HDL ratio, and triglycerides. At the end of the study, LI85008F supplementation also provided 21.26% (p?=?0.012) increase in serum adiponectin level, compared with the placebo group. No major adverse events were reported by the participants in the study duration. In addition, Adipokine profiling study in 3T3-L1 adipocytes demonstrates that LI85008F modulates key regulatory factors of adipogenic differentiation and insulin sensitivity, such as Adiponectin, Pref-1, and resistin.

Conclusion

The herbal formulation LI85008F (Adipromin) is prepared from commonly used medicinal plants extracts, which provides useful and safe application for weight loss in obese humans. It also demonstrates potential promise in controlling healthy blood glucose level in obesity linked type 2 diabetes.     

Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice

ABSTRACT: BACKGROUND: Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/-) mouse. METHODS: Spleen-derived MNCs were isolated from green fluorescent protein (GFP)-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC) or vehicle (Cuff-Vehicle) and were compared with sham-operated animals (Sham). RESULTS: The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 +/- 4; Vehicle, 20 +/- 4; Sham, 55 +/- 2 x103 mum2; p < 0.01). The animals that underwent the carotid cuff placement developed compensatory vessel enlargement, which was reduced by the MNC therapy. In addition, the treatment was able to reduce superoxide anion production, which likely contributed to the reduced apoptosis that was observed. Lastly, the immunofluorescence analysis revealed the presence of endothelial progenitor cells (EPCs) in the carotid endothelia of the apoE-/- mice. CONCLUSION: In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.     

Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice

Background  

The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice in both normal and ovariectomized conditions.     

Coenzyme Q intake elevates the mitochondrial and tissue levels of Coenzyme Q and alpha-tocopherol in young mice

The main objective of this study was to resolve the issue of whether the amounts of Coenzyme Q (CoQ), which is endogenously synthesized in cells, can be elevated in tissues and mitochondria of young mice by dietary supplementation with CoQ10. The prevalent view is that the uptake of exogenous CoQ by tissues other than plasma and liver either does not occur or is quite minimal. Mice, 6 mo of age, were fed 0, 148 or 654 mg CoQ10/(kg body x d) in their diets for 11 wk. CoQ10 intake enhanced both CoQ9 and CoQ10 homologues in the plasma, and in homogenates and mitochondria of liver, heart and skeletal muscle. CoQ was elevated in brain mitochondria, but not in the brain homogenate. The uptake of exogenous CoQ was higher in mitochondria of heart and skeletal muscle than those in liver. CoQ10 administration also elevated the alpha-tocopherol concentration in tissue homogenates and their mitochondria, thereby providing an in vivo indication of the "sparing" effect of CoQ on alpha-tocopherol. Results of this study demonstrate that, contrary to the historical view, both total and mitochondrial CoQ concentrations in the heart and skeletal muscle and in the mitochondria of brain of young mice can be augmented by dietary supplementation. Furthermore, CoQ intake enhances the antioxidative potential of tissues by elevating the endogenous amounts of alpha-tocopherol.     

Spirulina (Arthrospira) protects against cadmium-induced teratogenic damage in mice

The role of Spirulina (Arthrospira) in preventing cadmium (Cd) teratogenicity in ICR mice was studied. Cd was administered intraperitoneally to female mice at 1.5?mg/kg on gestation day (GD)-7, and Spirulina was given by peroral (intragastric) administration at 62.5, 125, 250, or 500?mg/kg from GD-0 through GD-17 (the day when animals were sacrificed). Because among the mechanisms suggested to account for reproductive damage are oxidative stress and lipoperoxidation, embryonic hydroperoxides were also determined. Treatment with Spirulina at the three highest doses significantly decreased the frequency of fetuses with exencephaly, micrognathia, and skeletal abnormalities induced by Cd. Furthermore, Spirulina treatment significantly and dose-dependently decreased lipid peroxidation, which was dramatically increased by administration of the metal. The results of the present study clearly point to the therapeutic potential of Spirulina in Cd-induced teratogenicity and probably through its antioxidant activity.     

Pinus pinaster oil affects lipoprotein metabolism in apolipoprotein E-deficient mice.

The aim of the present study was to assess the antiatherogenic properties of Pinus pinaster (maritime pine) seed oil. To this end, the effects of P. pinaster oil supplementation on lipoprotein levels and atherosclerotic lesions were compared to those of lard or sunflower oil in apolipoprotein E-deficient mice. Plasma total cholesterol (P < 0.0001) and VLDL + intermediary density lipoprotein (IDL)-cholesterol (P < 0.0001) levels were lower in mice fed P. pinaster and sunflower oil than in those fed the lard diet. In contrast, triglycerides (P < 0.0001) and VLDL + IDL-triglycerides (P < 0.0001) levels were higher in mice fed P. pinaster oil than sunflower oil or lard. The VLDL + IDL lipid composition of apolipoprotein E-deficient mice fed P. pinaster oil was intermediate between that of lard-fed transgenic mice and that of wild-type mice fed nonpurified diet. Using the Triton WR1339 method, the fractional catabolic rate of plasma triglycerides was found to be lower in mice fed P. pinaster oil (P < 0.0001) than sunflower oil or lard diet, suggesting a defective clearance of triglycerides in the P. pinaster group. Finally, the susceptibility of triglyceride-rich lipoproteins to in vitro lipoprotein lipase-mediated lipolysis was lower in the P. pinaster oil-fed group than in the lard-fed group. Despite the differences in VLDL + IDL level and lipid composition, the surface areas of aortic atherosclerotic lesions were not significantly different among mice fed P. pinaster, sunflower or lard diets. In conclusion, the results of the present study indicated that feeding P. pinaster oil had no better preventive effect on aortic atherosclerotic lesion extension in apolipoprotein E-deficient mice than other saturated or polyunsaturated fats.     

Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans

ObjectiveThe theoretically beneficial effects of coenzyme Q10 (Q10) on exercise-related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended by manufacturers influences these factors.MethodsUsing a randomized, double-blind, controlled design, we investigated the effect on physical capacity of 8 wk of treatment with a daily dose of 90 mg of Q10 (n = 12) compared with placebo (n = 11) in moderately trained healthy men 19 to 44 y old. Two days of individualized performance tests to physical exhaustion were performed before and after the intervention. Primary outcomes were maximal oxygen uptake, workload, and heart rate at the lactate threshold. Secondary outcomes were creatine kinase, hypoxanthine, and uric acid.ResultsNo significant differences between the groups were discerned after the intervention for maximal oxygen uptake (?0.11 L/min, 95% confidence interval ?0.31 to 0.08, P = 0.44), workload at lactate threshold (6.3 W, ?13.4 to 25.9, P = 0.36), or heart rate at lactate threshold (2.0 beats/min, ?4.9 to 8.9, P = 0.41). No differences between the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage).ConclusionAlthough in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate that such effects exist after supplementation with a recommended dose.     

Dried plums (prunes) reduce atherosclerosis lesion area in apolipoprotein E-deficient mice

Dried plums are a fruit high in pectin with substantial antioxidant activity. Previous studies in rats and man indicate that dried plums or plum fibre lower liver and plasma cholesterol, respectively. The apoE-deficient mouse, which develops atherosclerotic lesions rapidly when fed cholesterol, was used to determine the ability of dried plums to reduce atherosclerosis. Diets containing 0.15% cholesterol and either 0 (B+C), 4.75% (Lo DP) or 9.5% (Hi DP) dried plum powder were fed for 5 months. An additional group fed the basal diet without cholesterol (B-C) was included as a negative control. Arterial trees were dissected, stained to visualize lesions, and lesion area was quantitated by imaging software. Urinary thiobarbituric acid-reactive substances (TBARS) excretion and serum amyloid P-component (SAP) were measured as indicators of oxidative stress and inflammation, respectively. Final serum cholesterol was significantly increased and serum TAG decreased in the B+C group and dried plum groups relative to the B-C group. Percentage arterial tree atherosclerotic lesion area was significantly lower in the B-C and Lo DP groups compared to the B+C group (P<0.05), with a trend for a difference between the B+C and Hi DP groups (P=0.075). SAP concentration was significantly lower in the B-C and Lo DP groups with the Hi DP group trending lower than the B+C group. Urinary TBARS excretion did not differ among the groups. These results suggest that consuming dried plums may help slow the development of atherosclerosis.     

An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice

Black rice and its pigment fraction may have antiatherogenic activity, but the exact component contributing to the beneficial effect remains unclear. The aim of the present study was to investigate the influence of the anthocyanin-rich extract from black rice on the vulnerability of advanced plaques in apolipoprotein (apo) E-deficient mice. Using LC-MS, the anthocyanin-rich extract from black rice was identified as containing cyanidin-3-glucoside and peonidin-3-glucoside. ApoE-deficient mice (n = 30; 30 wk old) were randomly divided into 3 groups: a control group (fed the AIN-93G diet), the simvastin group [simva; fed the AIN-93G diet containing simvastatin, 50 mg/(kg.d)], or the anthocyanin-rich extract group [antho; fed the AIN-93G diet supplemented with anthocyanin-rich extract from black rice, 300 mg/(kg.d)]. After 20 wk of intervention, the plaque area that developed in the brachiocephalic artery of mice in the antho group was smaller than that of the control mice. Both the antho and simva groups had lower frequencies of the large necrotic core and thin fibrous cap in plaques than the control group. Collagen I was increased and matrix metalloproteinase-1 contents were reduced in the brachiocephalic lesion of both the antho and simva groups compared with the control group. Furthermore, mRNA levels of tissue factor and inducible nitric oxide synthase in aortae were decreased in the antho and simva groups. Supplementation of anthocyanin-rich extract improved the lipid profile by decreasing serum triglyceride, total cholesterol, and non-HDL cholesterol. These results suggest that chronic diet intake of anthocyanin-rich extract from black rice may enhance plaque stabilization in old apoE-deficient mice. The underlying mechanism is related mainly to inhibiting proinflammatory factors and improving the serum lipid profile.     

Coenzyme Q deficiency in mice following infection with Friend leukemia virus.

The specific activities of the succinate dehydrogenase-coenzyme Q reductase were assayed on mitochondrial preparations of this enzyme from spleen, liver, blood and peritoneal macrophages of mice infected with Friend leukemia virus, and of control mice. Significant increases in the deficiency of coenzyme Q-enzyme activity were found in the spleen and blood of infected animals as the infection progressed. No significant deficiency was observed in the liver or the peritoneal macrophages. The development of the deficiency and splenomegaly during infection seemingly correlate with previous data which showed that administration of coenzyme Q resulted in a reversal of splenomegaly and a reduction in mortality. A limiting factor in the resistance of mice to Friend leukemia virus appears to be the availability of coenzyme Q.