ubiquinone and Pulmonary-Disease--Chronic-Obstructive

COPD represents a major cause of mortality and morbidity worldwide, is linked to systemic inflammation and tends to coexist with a variety of comorbidities. Inflammation, oxidative stress and protease-antiprotease imbalance represent the pathogenic triad of COPD. Even though oxidative stress and mitochondrial dysfunction is a well-studied phenomenon in COPD and there is a variety of studies that aim to counteract its effect, there is limited data available on the use of coenzyme Q10 in COPD. The aim of the current review is to analyze the current data on the use of coenzyme Q10 in the management of COPD and frequently encountered comorbidities.

Topics: Humans; Inflammation; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Ubiquinone

Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O. One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured.. These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Antioxidants; Body Composition; Creatine; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Oxygen Inhalation Therapy; Physical Functional Performance; Pulmonary Disease, Chronic Obstructive; Time Factors; Ubiquinone; Walk Test

Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent airflow limitation. Pulmonary vascular endothelial barrier injury and inflammation are increasingly considered to be important pathophysiological processes in cigarette smoke extract (CSE)-induced COPD, but the mechanism remains unclear. To identify the cellular mechanism of endothelial barrier injury and inflammation in CSE-treated human umbilical vein endothelial cells (HUVECs), we investigated the effect of the mitochondrion-targeting antioxidant mitoquinone (MitoQ) on endothelial barrier injury and inflammation. We demonstrated that MitoQ restored endothelial barrier integrity by preventing VE-cadherin disassembly and actin cytoskeleton remodeling, as well as decreased inflammation by the NF-κB and NLRP3 inflammasome pathways in endothelial cells. In addition, MitoQ also maintained mitochondrial function by reducing the production of ROS and excess autophagy. Inhibition of autophagy by 3-MA protected against cytotoxicity that was induced by CSE in HUVECs. Overall, our study indicated that mitochondrial damage is a key promoter in the induction of endothelial barrier dysfunction and inflammation by CSE. The protective effect of MitoQ is related to the inhibition of ROS and excess autophagy in CSE-induced HUVEC injury.

Topics: Actins; Antigens, CD; Antioxidants; Autophagy; Cadherins; Cell Survival; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Inflammasomes; Inflammation; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Organophosphorus Compounds; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Smoke; Tobacco Products; Ubiquinone

Oxidative damage is a major contributing factor to carcinogenesis and obstructive disorders in lungs. Current evidence suggests that the inflammatory processes yield to oxidative mechanisms, which underlie COPD, lung cancer, and obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the oxidative damage in these diseases by evaluating the oxidative and antioxidant biomarkers.. Malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and coenzyme Q10 levels were evaluated in the blood samples of subjects with COPD, lung cancer, and OSAS by high-pressure liquid chromatography.. A total of 111 participants (35 females, 76 males) with OSAS (n = 29), COPD (n = 26), and lung cancer (n = 28) and healthy controls (n = 28) were included in the study. The malondialdehyde and coenzyme Q10 levels were significantly higher in all 3 diseases when compared with controls (P < .01), whereas 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were only significantly higher than in healthy controls in subjects with lung cancer (P = .005). The highest levels of malondialdehyde and coenzyme Q10 were determined in subjects with OSAS and lung cancer, respectively. The highest 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were also observed in subjects with lung cancer, but the differences of this biomarker with other diagnoses were not statistically significant (P = .56).. Oxidative damage was observed in all 3 diagnoses, and, as a response to oxidative stress, antioxidant mechanisms were also active in these diseases. Malondialdehyde and 8-oxo-7,8-dihydro-2'-deoxyguanosine were found to be efficiently usable in the evaluation of oxidative damage in chronic respiratory diseases. (ClinicalTrials.gov registration NCT02406053.).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Humans; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Ubiquinone

Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.. We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.. Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.. Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.. Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD.

Topics: Adult; Aged; Airway Remodeling; Animals; Antioxidants; Bronchial Hyperreactivity; Electron Transport Chain Complex Proteins; Female; Gene Expression Regulation; Humans; Hydrogen Peroxide; Male; Membrane Potential, Mitochondrial; Mice; Middle Aged; Mitochondria; Muscle, Smooth; Myocytes, Smooth Muscle; Organophosphorus Compounds; Oxidative Stress; Ozone; Pneumonia; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Respiratory System; Signal Transduction; Smoking; Ubiquinone

A low-T₃ syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ₁₀) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T₃ syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants.. We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), free-triiodotyronine (fT₃), free-tetraiodotyronine (fT₄), CoQ₁₀ (also corrected for cholesterol) and TAC. CoQ₁₀ was assayed by HPLC; TAC by the metmyoglobin-ABTS method and expressed as latency time (LAG) in radical species appearance.. We found significantly lower LAG values, fT₃ and fT₄ levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT₃ concentration. 12 out of 32 patients exhibited fT₃ levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT₃ concentration (normal fT₃ COPD and low fT₃ COPD). We observed lower LAG values in normal fT₃-COPD, compared to healthy subjects, with a further significant reduction in low fT₃-COPD patients. Moreover higher TSH concentration was present in normal fT₃-COPD, compared to healthy subjects, with a further significant increase in low fT₃-COPD patients. CoQ₁₀/cholesterol ratio was higher in low fT₃-COPD vs. normal fT₃-COPD, with a nearly significant difference.. These data seem to indicate an increased oxidative stress in low fT₃-COPD and a role of fT₃ in modulating antioxidant systems. However low fT₃ levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ₁₀ expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition.

Topics: Aged; Aged, 80 and over; Antioxidants; Cholesterol; Female; Humans; Hypothyroidism; Italy; Lung; Male; Middle Aged; Oxidative Stress; Prevalence; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Ubiquinone

Severity of chronic obstructive pulmonary disease (COPD) exacerbation is associated with increased level of copper (Cu), zinc (Zn), and lipid peroxidation (malodialdehyde, MDA). The aim of this study was to investigate the levels of lipid peroxidation, Coenzyme Q10 (CoQ10), Zn, and Cu in the COPD exacerbations. Forty-five patients with COPD acute exacerbation and 45 healthy smokers as control group were used in the study. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were lower in exacerbation group than in control. C- reactive protein levels, white blood cell count, and sedimentation rate were significantly (p<0.001) higher in patients than in control. CoQ10 level and Cu/Zn ratio was significantly (p<0.05) lower in patients than in control, although MDA, Cu, and Zn levels were significantly (p<0.05) higher in patients than in control. Negative correlations were found among MDA, Cu, Zn, FEV1, and FVC values in exacerbation and control subjects (p<0.05). In conclusion, we observed that oxidative stress in the exacerbation period of COPD patients was increased. The decrease in CoQ10 level and Cu/Zn ratio and elevation in Cu and Zn levels observed in the patients probably result from the defense response of organism and are mediated by inflammatory-like substances.

Topics: Aged; Copper; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Ubiquinone; Zinc

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q 10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. On the other hand, a low-T3 syndrome, due to reduced peripheral conversion from the prohormone T4, is observed in different chronic diseases: this condition is considered an adaptation mechanism, usually not to be corrected by replacement therapy. In order to perform a metabolic evaluation, we have studied a group of 15 patients, aged 69-82 ys, affected by chronic obstructive pulmonary disease (COPD), comparing respiratory indexes, thyroid hormones and CoQ10 levels (also normalized with cholesterol levels) in patients with low (group A) or normal (group B) free-T3 (FT3) concentrations. We found that CoQ10 levels were significantly higher in patients of group A than in B (0.91+/- 0.03 vs 0.7 +/- 0.04 microg/ml respectively); the same difference was observed when comparing the ratios between CoQ10/cholesterol in the two groups (200.16 +/- 8.96 vs 161.08 +/- 7.03 nmol/mmol respectively). These preliminary data seem to indicate that low T3 levels are accompanied by metabolic indexes of a true hypothyroidism in COPD patients. Whether this datum supports the need to perform a replacement therapy in such a condition requires further studies.

Topics: Aged; Aged, 80 and over; Coenzymes; Humans; Oxygen; Partial Pressure; Pulmonary Disease, Chronic Obstructive; Thyroid Hormones; Triiodothyronine; Ubiquinone