coenzyme-q10 and Diabetic-Nephropathies

The diabetic kidney disease (DKD) has become a seriously kidney disease that commonly caused by diabetes mellitus (DM). Oxidative stress response plays an essential role in the genesis and worsening of DKD and Coenzyme Q10 (CoQ10) has been reported the promising clinical effectiveness on DKD treatment. However, there is lack of relative evidence-based medical evidence currently.. The systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, which conducted to evaluate the effectiveness of CoQ10 in combination with other western medicine for DKD therapy through the randomized controlled trials (RCTs) and experimental studies.. RCTs and experimental studies were searched based on standardized searching rules in 12 medical databases from the inception up to June 2018 and a total of 8 articles (4 RCTs and 4 experimental studies) were enrolled in the meta-analysis.. The results revealed that CoQ10 combined with other western medicine show statistical differences in the laboratory parameters of fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and malondialdehyde (MDA) amelioration after DKD therapy compared with control group. However, LDL-C and Urea level for RCTs and Urine output and Glucose for experimental studies on DKD was not superior to control group.. We need to make conclusion cautiously for the effectiveness of CoQ10 application on DKD therapy. More standard, multicenter, double-blind RCTs, and formal experimental studies of CoQ10 treatment for DKD were urgent to be conducted for more clinical evidence providing in the future. The underlying pharmacological mechanism of CoQ10 needs to be researched and revealed for its future application on DKD therapy.

Topics: Blood Glucose; Cholesterol; Diabetic Nephropathies; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone; Vitamins

Data on the effects of coenzyme Q10 (CQ10) on gene expression related to insulin, lipid, and inflammation in patients with diabetic nephropathy (DN) are scarce. This study aimed to determine the effects of CQ10 supplementation on gene expression related to insulin, lipid, and inflammation pathways in patients with DN.. Forty patients with DN, aged 40 to 85 years old, were randomly assigned into 2 groups to receive either 100 mg/d of CQ10 supplements (n = 20) or placebo (n = 20), for 12 weeks. Gene expression related to signaling pathway of insulin, lipid, and inflammation were determined in blood samples using a reverse transcriptase polymerase chain reaction method.. Quantitative results of reverse transcriptase polymerase chain reaction demonstrated that compared with the placebo, CQ10 administration upregulated gene expression of peroxisome proliferator-activated receptor-γ (P = .02) in peripheral blood mononuclear cells of the patients with DN. In addition, compared with the placebo, CQ10 supplementation downregulated gene expression of interleukin-1 (P = .003) and tumor necrosis factor-α (P = .02). No significant effects were observed on gene expression of oxidized low-density lipoprotein, lipoprotein(a), glucose transporter-1, transforming growth factor-β in the CQ10 group.. Overall, CQ10 supplementation for 12 weeks in DN patients significantly improved gene expression of peroxisome proliferator-activated receptor-γ, interleukin-1, and tumor necrosis factor-α.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Diabetic Nephropathies; Dietary Supplements; Double-Blind Method; Female; Gene Expression Regulation; Humans; Inflammation Mediators; Insulin; Interleukin-1; Iran; Lipid Metabolism; Male; Middle Aged; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Ubiquinone

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 nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183±1.7nm and a negative zeta potential of -25.3mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip+UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip+UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/- UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Liposomes; Male; Microbubbles; Rats; Rats, Sprague-Dawley; Theranostic Nanomedicine; Ubiquinone

This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with sitagliptin in experimentally induced diabetic nephropathy. The diabetic rats were treated with coenzyme Q10 or sitagliptin and their concomitant administration. Various parameters of renal function like serum creatinine, urea, uric acid and markers of oxidative stress such as renal malondialdehyde content (MDA), glutathione (GSH) level and superoxide dismutase (SOD), catalase activities were measured. TNF-α, TGF-β, MPO activity and nitrite content were estimated in renal tissue with histopathological observation. Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum creatinine, urea and uric acid levels. Streptozotocin-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and GSH level. In addition, TNF-α, TGF- β, MPO activity and nitrite content were significantly increased in diabetic rats. Treatment with coenzyme Q10 or sitagliptin and their co-administration ameliorated STZ-nicotinamide-induced renal damage which was reflected by decreased oxidative stress, TNF-α, TGF-β, MPO activity, nitrite content along with histopathological changes. To conclude, concomitant administration of coenzyme Q10 and sitagliptin showed a better renoprotective effect than coenzyme Q10 or sitagliptin when given alone.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Kidney Function Tests; Oxidative Stress; Protective Agents; Rats; Sitagliptin Phosphate; Treatment Outcome; Ubiquinone

Cardiovascular benefits of ubiquinone have been previously demonstrated, and we administered it as a novel therapy in an experimental model of type 2 diabetic nephropathy. db/db and dbH mice were followed for 10 weeks, after randomization to receive either vehicle or ubiquinone (CoQ10; 10mg/kg/day) orally. db/db mice had elevated urinary albumin excretion rates and albumin:creatinine ratio, not seen in db/db CoQ10-treated mice. Renal cortices from db/db mice had lower total and oxidized CoQ10 content, compared with dbH mice. Mitochondria from db/db mice also contained less oxidized CoQ10(ubiquinone) compared with dbH mice. Diabetes-induced increases in total renal collagen but not glomerulosclerosis were significantly decreased with CoQ10 therapy. Mitochondrial superoxide and ATP production via complex II in the renal cortex were increased in db/db mice, with ATP normalized by CoQ10. However, excess renal mitochondrial hydrogen peroxide production and increased mitochondrial membrane potential seen in db/db mice were attenuated with CoQ10. Renal superoxide dismutase activity was also lower in db/db mice compared with dbH mice. Our results suggest that a deficiency in mitochondrial oxidized CoQ10 (ubiquinone) may be a likely precipitating factor for diabetic nephropathy. Therefore CoQ10 supplementation may be renoprotective in type 2 diabetes, via preservation of mitochondrial function.

Topics: Adenosine Triphosphate; Albuminuria; Animals; Citrate (si)-Synthase; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Hepatitis A Virus Cellular Receptor 1; Kidney; Kidney Function Tests; Membrane Potential, Mitochondrial; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Oxidation-Reduction; Random Allocation; Reactive Oxygen Species; Ubiquinone

Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes.. Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.. Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).. db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Glomerular Filtration Rate; Guanosine Diphosphate; Ion Channels; Kidney Glomerulus; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Oxygen Consumption; Proteinuria; Ubiquinone; Uncoupling Protein 2; Vitamins