ubiquinone and Diabetic-Retinopathy

To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy (NPDR) in a randomized, double-blind, phase IIa, placebo-controlled, clinical trial. Three groups of 20 patients were formed: Group 1, ubiquinone; Group 2, combined therapy; and Group 3, placebo (one daily dose for 6 months).. Fluidity of the submitochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer (Im) and excimer (Ie). Hydrolytic activity of the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method.. Normal, baseline submitochondrial membrane fluidity, 0.24 ± 0.01 Ie/Im, was significantly diminished in the three study groups vs. normal values (P < 0.0001); placebo, 0.14 ± 0.01 Ie/Im; ubiquinone, 0.14 ± 0.01 Ie/Im; and combined therapy, 0.13 ± 0.00 Ie/Im. Afterward, it increased significantly (P < 0.0001), the ubiquinone group 0.22 ± 0.01 Ie/Im, combined therapy group, 0.19 ± 0.01 Ie/Im; with no changes the placebo group. Baseline hydrolytic activity of the F0F1-ATPase enzyme increased in the three study groups vs. normal values (184.50 ± 7.84 nmol PO4), placebo, 304.12 ± 22.83 nmol PO4 (P < 0.002); ubiquinone, 312.41 ± 25.63 nmol PO4 (P < 0.009); and combined therapy, 371.28 ± 33.50 nmol PO4 (P < 0.002). Afterward, a significant decrease the enzymatic activity: ubiquinone, 213.25 ± 14.19 nmol PO4 (P < 0.001); and combined therapy, 225.55 ± 14.48 nmol PO4 (P < 0.0001).. Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants.

Topics: Antioxidants; Catalase; Diabetic Retinopathy; Double-Blind Method; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Middle Aged; Mitochondria; Nitrates; Nitrites; Ubiquinone

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

Topics: Antioxidants; Catalase; Diabetic Retinopathy; Double-Blind Method; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Ubiquinone

The aim was to evaluate circulating levels of reactive oxygen species (ROS) and changes in central macular thickness (CMT) in patients with nonproliferative diabetic retinopathy (NPDR) after antioxidant supplementation.. A total of 68 patients (68 eyes) with NPDR were enrolled. Patients were randomly divided into two groups: Treated with antioxidant supplement (Group A) and untreated control group (Group B). Each tablet, for oral administration, containing pycnogenol 50 mg, Vitamin E 30 mg and coenzyme Q10 20 mg. CMT and free oxygen radical test (FORT) were analyzed at baseline (T0), 3 (T1) and 6 (T2) months in both groups.. In Group A, FORT levels and CMT were significantly reduced over time (P < 0.001 for both). In Group B, FORT levels were increased (P < 0.001) and CMT did not vary significantly (P = 0.81) over 3 time points.. This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy. Moreover, our findings have suggested also an influence on retinal thickness.

Topics: Adjuvants, Immunologic; Adult; Aged; Antioxidants; Biomarkers; Diabetic Retinopathy; Dietary Supplements; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Flavonoids; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Plant Extracts; Reactive Oxygen Species; Retina; Time Factors; Tomography, Optical Coherence; Ubiquinone; Visual Acuity; Vitamin E; Vitamins

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Topics: Adult; C-Peptide; Coenzymes; Deafness; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; DNA, Mitochondrial; Family Health; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Hearing; Humans; Lactic Acid; Male; Middle Aged; Mothers; Point Mutation; Time Factors; Treatment Outcome; Ubiquinone

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5-8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58-80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.

Topics: Animals; Antioxidants; Diabetic Retinopathy; Male; Mitochondria; Oligopeptides; Rats; Rats, Long-Evans; Ubiquinone; Vision, Ocular