ubiquinone and Non-alcoholic-Fatty-Liver-Disease

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of

Topics: Antioxidants; Berberine; Curcumin; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Meta-Analysis as Topic; Non-alcoholic Fatty Liver Disease; Obesity; Observational Studies as Topic; Plant Extracts; Probiotics; Randomized Controlled Trials as Topic; Resveratrol; Salvia miltiorrhiza; Silymarin; Ubiquinone; Vitamin D; Vitamin E; Xanthophylls

Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties. NAFLD has been shown to be associated with disturbances in plasma and liver CoQ concentrations, but the relationship between these changes and disease development and progression is not yet clear. Dietary supplementation with CoQ has been found to be hepatoprotective and to reduce oxidative stress and inflammation as well as improving mitochondrial dysfunction, suggesting that it may be beneficial in NAFLD. However, studies using animal models or patients with NAFLD have given inconclusive results. Overall, evidence is now emerging to indicate that disturbances in CoQ metabolism are involved in NAFLD development and progression to NASH, and this highlights the need for further studies with human subjects to fully clarify its role.

Topics: Animals; Dietary Supplements; Humans; Inflammation; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Ubiquinone

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production; antioxidant therapy is one of the main therapeutic lines in NAFLD. In the current study we aimed to investigate the effect of coenzyme Q10 (coQ10) therapy on several adipocytokines and insulin resistance in patients with NAFLD.. In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled. After randomization into two groups, 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks. BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose (FSG), insulin resistance (IR), vaspin, chemerin, pentraxin 3 (PTX3) and markers of oxidative stress including total antioxidant capacity (TAC) and malondialdehyde (MDA).. After 4 weeks of coQ10 supplementation, waist circumference (WC) and serum AST and TAC concentrations significantly decreased in intervention group (p <0.05) but no significant changes occurred in placebo-treated group. In stepwise multivariate linear regression model, change in serum FSG was a significant predictor of changes in serum vaspin, chemerin and pentraxin 3 (p <0.001).. The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD. Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit.

Topics: Adipokines; Adult; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokines; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Serpins; Serum Amyloid P-Component; Ubiquinone; Waist Circumference; Young Adult

Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%).. Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups.. NCT03017235.. The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.. Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common.. In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.. Postoperative CRP elevation was a better predictor of prognosis in patients with gastric cancer than the occurrence of intra-abdominal infectious complications.. In clinical practice, mixed-species malaria infections are often not detected by light microscopy (LM) or rapid diagnostic test, as a low number of parasites of one species may occur. Here, we report the case of an 8-year-old girl migrating with her family from Afghanistan with a two-species mixed infection with

Topics: 3-Hydroxybutyric Acid; Acetazolamide; Acrylates; Administration, Intravenous; Adolescent; Adult; Aerosols; Afghanistan; Aflatoxin M1; Agaricales; Aged; Aged, 80 and over; Agricultural Irrigation; Air Pollutants; alpha-L-Fucosidase; Amino Acid Sequence; Androgen Antagonists; Animals; Antibodies, Bacterial; Antigens, Bacterial; Antineoplastic Agents; Antioxidants; Apoptosis; Artifacts; Autophagy; B7-H1 Antigen; Bacterial Proteins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Bile; Bioelectric Energy Sources; Biosensing Techniques; Body Mass Index; Brain; Brazil; Breast Neoplasms; Bufo arenarum; Burkholderia; C-Reactive Protein; Cadmium; Carbon Compounds, Inorganic; Carbon-13 Magnetic Resonance Spectroscopy; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Carcinoma, Transitional Cell; Case-Control Studies; CD4-Positive T-Lymphocytes; Cell Count; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Characiformes; Child; China; Cities; Cobalt; Colonic Neoplasms; Copper Sulfate; Cross-Sectional Studies; Cyclin-Dependent Kinase Inhibitor p16; Cytokines; Deoxycytidine; Diagnosis, Differential; Digestive System; Dihydroxyphenylalanine; Disease Models, Animal; DNA (Cytosine-5-)-Methyltransferase 1; DNA Barcoding, Taxonomic; DNA, Bacterial; Dose-Response Relationship, Drug; Down-Regulation; Edetic Acid; Electrochemical Techniques; Electrodes; Embolization, Therapeutic; Embryo, Nonmammalian; Environmental Monitoring; Enzyme-Linked Immunosorbent Assay; Epithelial-Mesenchymal Transition; Fatty Acids; Feces; Female; Follow-Up Studies; Food Contamination; Forkhead Box Protein M1; Fresh Water; Fungicides, Industrial; Gallium Isotopes; Gallium Radioisotopes; Gastrectomy; Gastric Bypass; Gastric Outlet Obstruction; Gastroplasty; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Bacterial; Genetic Markers; Genome, Bacterial; Genome, Mitochondrial; Glioma; Glycogen Synthase Kinase 3 beta; Goats; Gonads; Guatemala; Halomonadaceae; HEK293 Cells; Helicobacter Infections; Helicobacter pylori; Hepacivirus; Histone-Lysine N-Methyltransferase; Hormones; Humans; Hydroxybutyrate Dehydrogenase; Hypersplenism; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Iran; Japan; Lactuca; Laparoscopy; Larva; Ligands; Liver Neoplasms; Lymphocyte Activation; Macrophages; Malaria; Male; Mercury; Metabolic Syndrome; Metals, Heavy; Mice; Middle Aged; Milk, Human; Mitochondria; Models, Molecular; Molecular Structure; Mothers; Multilocus Sequence Typing; Muscles; Mutation; Nanocomposites; Nanotubes, Carbon; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Neuroimaging; Nitriles; Nitrogen Isotopes; Non-alcoholic Fatty Liver Disease; Nuclear Magnetic Resonance, Biomolecular; Obesity; Obesity, Morbid; Oligopeptides; Oxidation-Reduction; Pancreatic Neoplasms; Particle Size; Particulate Matter; Pepsinogen A; Pesticides; Pharmacogenetics; Phosphatidylinositol 3-Kinases; Phospholipids; Phylogeny; Plasmodium ovale; Plasmodium vivax; Platelet Count; Polyhydroxyalkanoates; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postoperative Complications; Pregnancy; Prevalence; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Domains; Proto-Oncogene Proteins c-akt; Proton Magnetic Resonance Spectroscopy; Pseudogenes; PTEN Phosphohydrolase; Pyrazoles; Pyrimidines; Radiographic Image Interpretation, Computer-Assisted; Radiopharmaceuticals; Rats, Long-Evans; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Receptor, Notch3; Receptors, G-Protein-Coupled; Receptors, Urokinase Plasminogen Activator; Recombinant Proteins; Repressor Proteins; Resveratrol; Retrospective Studies; Risk Assessment; Risk Factors; RNA, Messenger; RNA, Ribosomal, 16S; Salinity; Salvage Therapy; Seasons; Sequence Analysis, DNA; Seroepidemiologic Studies; Signal Transduction; Skin; Snails; Soluble Guanylyl Cyclase; Solutions; Spain; Species Specificity; Spheroids, Cellular; Splenic Artery; Stomach Neoplasms; Streptococcus pneumoniae; Structure-Activity Relationship; Sulfonamides; Sunlight; Surface Properties; Surgical Instruments; Surgical Wound Infection; Survival Rate; Tetrahydrouridine; Thinness; Thrombocytopenia; Tissue Distribution; Titanium; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Turkey; Ubiquinone; Urologic Neoplasms; Viral Envelope Proteins; Wastewater; Water Pollutants, Chemical; Weather; Wnt Signaling Pathway; Xenograft Model Antitumor Assays; Young Adult

Shc expression rises in human nonalcoholic steatohepatitis (NASH) livers, and Shc-deficient mice are protected from NASH-thus Shc inhibition could be a novel therapeutic strategy for NASH. Idebenone was recently identified as the first small-molecule Shc inhibitor drug. We tested idebenone in the fibrotic methionine-choline deficient (MCD) diet and the metabolic fast food diet (FFD) mouse models of NASH. In the fibrotic MCD NASH model, idebenone reduced Shc expression and phosphorylation in peripheral blood mononuclear cells and Shc expression in the liver; decreased serum alanine aminotransferase and aspartate aminotransferase; and attenuated liver fibrosis as observed by quantitative polymerase chain reaction (qPCR) and hydroxyproline quantification. In the metabolic FFD model, idebenone administration improved insulin resistance, and reduced inflammation and fibrosis shown with qPCR, hydroxyproline measurement, and histology. Thus, idebenone ameliorates NASH in two mouse models. As an approved drug with a benign safety profile, Idebenone could be a reasonable human NASH therapy.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Choline Deficiency; Diet; Disease Models, Animal; Fast Foods; Leukocytes, Mononuclear; Liver; Liver Cirrhosis; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phosphorylation; Protective Agents; Shc Signaling Adaptor Proteins; Signal Transduction; Therapeutics; Ubiquinone

Topics: Ascorbic Acid; Diet, Reducing; Humans; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Selenomethionine; Silymarin; Ubiquinone; Vitamin E

Coenzyme Q10 (CoQ10) is a well-known anti-adipogenic factor that possesses the capability to regulate non-alcoholic fatty liver disease (NAFLD). However, the mechanism by which CoQ10 acts on NAFLD is still unclear. In this study, the role of CoQ10 in the prevention of NAFLD was investigated in vivo and in vitro. C57BL/6J mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with CoQ10 (1800 mg kg-1 HFD) for 24 weeks. HepG2 cells were treated with sodium palmitate for investigating the mechanism of action of CoQ10 on NAFLD. The results showed that CoQ10 alleviated HFD-induced weight gain and NAFLD, accompanied by an anti-hyperlipidaemia effect, by reducing the serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Importantly, CoQ10 could downregulate the expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), which are related to lipid synthesis, and upregulate the expression of peroxisome proliferator-activated receptors α (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) associated with fatty acid oxidation. Similar to the results from mice, treatment with CoQ10 alleviated sodium palmitate-induced hepatocyte steatosis via the inhibition of lipogenesis and promotion of fatty acid oxidation. However, Compound C, as an AMPK inhibitor, could significantly block the benefits derived from CoQ10 treatment. In conclusion, CoQ10 could serve as an AMPK activator and regulate the hepatic lipid metabolism to inhibit the abnormal accumulation of hepatic lipids and prevent NAFLD progression.

Topics: AMP-Activated Protein Kinases; Animals; Cell Proliferation; Diet, High-Fat; Gene Expression Regulation; Hep G2 Cells; Humans; Lipid Peroxidation; Lipids; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Ubiquinone

Current peroxisome proliferator-activated receptor (PPAR)-targeted drugs, such as the PPARγ-directed diabetes drug rosiglitazone, are associated with undesirable side effects due to robust agonist activity in non-target tissues. To find new PPAR ligands with fewer toxic effects, we generated transgenic zebrafish that can be screened in high throughput for new tissue-selective PPAR partial agonists. A structural analog of coenzyme Q

Topics: 3T3-L1 Cells; Animals; Animals, Genetically Modified; Benzoquinones; Drug Evaluation, Preclinical; HEK293 Cells; Humans; Ligands; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR gamma; Ubiquinone; Zebrafish

Topics: Alanine Transaminase; Alkaline Phosphatase; Ammonia; Animals; Aspartate Aminotransferases; Bilirubin; Biomarkers; Brain-Derived Neurotrophic Factor; Choline; Choline Deficiency; Diet; Dose-Response Relationship, Drug; gamma-Glutamyltransferase; Interleukin-6; Liver; Male; Methionine; Neuroprotective Agents; Nitric Oxide; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar; Serum Albumin; Ubiquinone

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

Topics: Animals; Dietary Fats; Lipoproteins, LDL; Male; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Sulfhydryl Compounds; Ubiquinone