ubiquinol and Hyperlipidemias

To assess the effects of fenofibrate therapy on concentrations of plasma ubiquinol-10 and ubiquinone-10-the reduced and oxidized forms, respectively, of coenzyme Q(10).. Prospective, open-label, non-controlled study.. University clinic and laboratory.. Eighteen patients with hyperlipidemia and type 2 diabetes mellitus.. Patients received fenofibrate 150 mg/day for 12 weeks.. Metabolic parameters were assessed 4, 8, and 12 weeks after the start of fenofibrate treatment. Plasma ubiquinol-10 and ubiquinone-10 levels were measured by reverse-phase high-performance liquid chromatography. At 4, 8, and 12 weeks, significant reductions in fasting triglyceride levels and significant increases in high-density lipoprotein cholesterol levels were noted. Total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and adiponectin levels, however, did not change significantly. Plasma ubiquinol-10 concentrations significantly increased after 8 and 12 weeks (p<0.05 for both), whereas ubiquinone-10 concentrations tended to decrease, especially at 12 weeks.. Our findings suggest that fenofibrate may help produce energy or prevent oxidation by increasing plasma ubiquinol-10 concentration; this effect may protect against the development and progression of atherosclerosis. In addition, treatment with fenofibrate demonstrated a favorable effect on serum lipid parameters.

Topics: Coenzymes; Diabetes Mellitus, Type 2; Disease Progression; Female; Fenofibrate; Humans; Hyperlipidemias; Male; Middle Aged; Prospective Studies; Ubiquinone

It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the ba

Topics: Antioxidants; Atorvastatin; Catalase; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Erythrocytes; Fatty Acids, Unsaturated; Glutathione; Glutathione Peroxidase; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lymphocytes; Male; Middle Aged; Pravastatin; Pyrroles; Simvastatin; Superoxide Dismutase; Ubiquinone; Vitamin E

Ubiquinol-10 and ubiquinone-10 were measured in plasma of patients with several pathologies known to be associated with increased oxidative stress. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10, was found to be significantly lower in hyperlipidaemic patients and in patients with liver diseases than in age-matched control subjects. In contrast, no decrease in ubiquinol-10 was detected in plasma of patients with coronary heart disease and Alzheimer's disease. Except for ubiquinol-10, no other lipophilic antioxidant was found to be decreased in patients with liver diseases. These data suggest that the level of ubiquinol-10 in human plasma may serve as a marker for liver dysfunction, reflecting its diminished reduction by the liver rather than increased consumption by oxidants.

Topics: Adult; Aged; Alzheimer Disease; Biomarkers; Cholesterol; Coronary Disease; Humans; Hyperlipidemias; Liver Diseases; Middle Aged; Models, Biological; Oxidative Stress; Reference Values; Reproducibility of Results; Triglycerides; Ubiquinone

Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10), is a potent lipophilic antioxidant present in nearly all human tissues. The exceptional oxidative lability of ubiquinol-10 implies that it may represent a sensitive index of oxidative stress. The present study was undertaken to assess the hypothesis that the level of ubiquinol-10 in human plasma can discriminate between healthy subjects and patients who are expected to be subjected to an increased oxidative stress in vivo. Using a newly developed method, we measured plasma ubiquinol-10 in 38 hyperlipidaemic patients with and without further complications, such as coronary heart disease, hypertension, or liver disease, and in 30 healthy subjects. The oxidizability of plasma samples obtained from hyperlipidaemic patients was found to be increased in comparison with control subjects, suggesting that the patients were subjected to a higher oxidative stress in vivo than the controls. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10 or normalized to plasma lipids, was lower in the patients than in controls (P = 0.001 and 0.008, respectively). The proportion of ubiquinol-10 decreased in the order young controls > aged controls > hyperlipidaemic patients without complications > hyperlipidaemic patients with complications (P = 0.003). A negative correlation was found between the proportion of ubiquinol-10 and plasma triglycerides. The hyperlipidaemic patients with hypertension had a lower proportion of ubiquinol-10 than subjects without. When the study population was divided into smokers and non-smokers, plasma ubiquinol-10 was found to be reduced amongst smokers, independently of whether it was expressed as a percentage of total ubiquinol-10 + ubiquinone-10 (P = 0.006) or normalized to plasma lipids (P = 0.009). These data suggest that the level of ubiquinol-10 in human plasma may represent a sensitive index of oxidative stress in vivo especially indicative of early oxidative damage. Measuring plasma ubiquinol-10 can be proposed as a practical approach to assess oxidative stress in humans.

Topics: Adult; Alcohol Drinking; Amidines; Antidotes; Body Mass Index; Coronary Disease; Female; Humans; Hyperlipidemias; Hypertension; Lipid Peroxidation; Lipoxygenase; Liver Diseases; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Regression Analysis; Risk Factors; Smoking; Spectrophotometry; Triglycerides; Ubiquinone

Lipoprotein oxidation induced in vitro in whole plasma is expected to be a more relevant model of the lipoprotein oxidation in the arterial wall than the in vitro oxidation of single isolated lipoproteins, e.g., low density lipoprotein (LDL). However, it is unclear, whether the oxidizability of whole plasma may serve as an adequate measure of the oxidizability of plasma lipoproteins. We measured the oxidizability of whole plasma diluted 150-fold as an absorbance increase at 234 nm known to reflect the level of conjugated dienes in the samples. Plasma oxidation was induced by Cu(II), 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH), lipoxygenase or myeloperoxidase+H2O2. Oxidizability of human plasma measured in the presence of Cu(II) was found to correlate with the oxidizability of LDL measured in the common Cu(II)-based LDL oxidation assay. The plasma oxidizability also correlated positively with plasma oxidizable fatty acid and negatively with plasma antioxidant content. Supplementation of human plasma with different antioxidants (albumin, urate, ascorbate, bilirubin, alpha-tocopherol and ubiquinol-10) in vitro decreased its oxidizability. Supplementation of Watanabe heritable hyperlipidaemic rabbits with different antioxidants (vitamin E, ubiquinone-10, probucol, carvedilol) in vivo lowered the oxidizability of rabbit plasma in comparison with rabbits fed standard diet. When plasma from hyperlipidaemic patients with or without coronary heart disease and from age-matched healthy controls was studied, the plasma oxidizability was found to be highest in the patients with coronary heart disease and lowest in the controls. Taken together, these data indicate that the plasma oxidation assay (i) provides information similar to that obtained using the common LDL oxidation assay, (ii) upgrades the latter, taking into account the effect of hydrophilic antioxidants on lipoprotein oxidation and characterizing the oxidizability of all plasma lipoproteins, and (iii) offers important practical advantages, such as fast and simple sample processing, low amount of plasma required and avoidance of artefactual oxidation during lipoprotein isolation. We propose the measurement of plasma oxidizability at 234 nm as an adequate practical index of the oxidizability of plasma lipoproteins.

Topics: Amidines; Animals; Antioxidants; beta Carotene; Carotenoids; Copper; Fatty Acids, Nonesterified; Humans; Hydrogen Peroxide; Hyperlipidemias; Lipoproteins; Lipoproteins, LDL; Lipoxygenase; Oxidants; Oxidation-Reduction; Peroxidase; Rabbits; Regression Analysis; Ubiquinone; Vitamin E

Plasma ubiquinol was measured in diabetics, patients on haemodialysis (HD) therapy, patients maintained by continuous ambulatory peritoneal dialysis (CAPD), hyperlipidaemic patients and control subjects. Ubiquinol values were standardized using total cholesterol (mumol/mmol). Diabetics, HD and CAPD patients were found to have plasma ubiquinol levels which were lower than the control subjects. There was no difference in values between the control subjects and hyperlipidaemic patients. Values for diabetics with poor metabolic control were similar to those with good control, and patients with diabetic complications had values which were not significantly different from those for patients with no complications. IDDM patients were found to have values which were lower than the control group, whereas values for the NIDDM patients were not significantly different. These results suggest that increased oxidative stress in certain patient groups may be the result of, and/or the cause of, decreased plasma ubiquinol. This could be due to increased demand or to decreased ability to regenerate the effective form of antioxidant.

Topics: Adolescent; Adult; Aged; Cholesterol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Male; Middle Aged; Oxidative Stress; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Triglycerides; Ubiquinone