ubiquinone and Pneumonia

Cigarette smoking, which induces airway inflammation and mucus hypersecretion, is a major risk factor for the development of cigarette smoke (CS)-induced airway disorders. In this study, we investigated the effects and mechanisms of mitoquinone (MitoQ), a mitochondria-targeted antioxidant, on CS-induced airway inflammation and mucus hypersecretion in mice.. C57BL/6J mice were exposed to CS for 75 min twice daily, 5 days per week for 4 weeks. MitoQ (2.5, 5 mg/kg/day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was obtained for cell counting and determination of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination; Western blotting was used to measure levels of Mfn2, Drp1, cytochrome c, NF-κB p65, and IκBα.. Pretreatment with MitoQ significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, goblet cell hyperplasia and Muc5ac staining. The numbers of total cells, neutrophils and macrophages, as well as levels of TNF-α and IL-6 in BALF were remarkably decreased by MitoQ in a dose-dependent manner. MitoQ attenuated oxidative stress by preventing the CS-induced increase in malondialdehyde level and decrease in superoxide dismutase activity and GSH/GSSG ratio. MitoQ decreased the expression of mitochondrial fission protein Drp1 and increased that of mitochondrial fusion protein Mfn2, as well as reduced cytochrome c release into the cytosol. Furthermore, MitoQ suppressed IκBα degradation and NF-κB p65 nuclear translocation.. MitoQ attenuates inflammation, mucus hypersecretion, and oxidative stress induced by CS. It may exert these effects in part by modulating mitochondrial function and the NF-κB signal pathway.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cytokines; Disease Models, Animal; Inflammation Mediators; Lung; Male; Mice, Inbred C57BL; Mitochondria; Mucus; NF-kappa B; Organophosphorus Compounds; Oxidative Stress; Pneumonia; Secretory Pathway; Signal Transduction; Smoke; Tobacco Products; 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 61-year-old woman began to take a dietary supplement contained CoQ10 and perilla leaf extract. Two months later, a dry cough appeared. The number of eosinophils in peripheral blood was elevated and chest radiograph images showed infiltrative shadows in the left middle lung. A chest CT scan showed consolidation in the left upper lobe (S3) and lower lobe (S10). The percentage of eosinophils was abnormally high in bronchoalveolar lavage fluid (BALF), and examination of a transbronchial lung biopsy (TBLB) specimen showed marked infiltration of eosinophils in the alveolar wall. Drug lymphocyte stimulation test (DLST) indicated high stimulation index for both supplement containing CoQ10 and its element of CoQ10. We diagnosed drug-induced pneumonitis, caused by CoQ10. The symptoms of the patient and pulmonary infiltrative shadows on chest radiograph improved after she stopped taking the supplements and started taking prednisolone orally. Recently various dietary supplements are coming onto the market. Since the possible adverse effects of these supplements are not investigated extensively, care should be taken for symptoms relating to food supplements.

Topics: Coenzymes; Dietary Supplements; Female; Humans; Lymphocyte Activation; Middle Aged; Pneumonia; Prednisolone; Pulmonary Eosinophilia; Treatment Outcome; Ubiquinone

Radiation pneumonitis are well recognized as complications of radiotherapy for the thoracic malignancies. However, the pathogenesis of radiation pneumonitis has been poorly understood and prevention of it has not been developed. In this study, to define the mechanisms of radiation pneumonitis biologically, we measured lipid peroxides, the activities of glutathione peroxidase (GSH pex.), leukotriene C4 and D4 (LTC4 and LTD4) in the irradiated lungs of mice. Eight weeks old female ICR mice were sacrificed at various time periods (immediately after to 5 days) following the 10 Gy whole-body irradiation with 60Co gamma rays. The lipid peroxides and the activities of GSH pex. increased immediately after the irradiation, but returned to the control level 1 hour after the irradiation. And then, the lipid peroxides also increased from 1 day after the irradiation, while the activities of GSH pex. decreased below the control level. LTC4 and LTD4 in the irradiated lungs of mice were also significantly higher than those of non-irradiated controls. Furthermore, we investigated effects of Coenzyme Q10 and Azelastine for the prevention of radiation pneumonitis. Lungs of ICR mice after 10 Gy whole-thorax irradiation treated with those drugs were compared with the control lungs pathologically. Intraperitoneal administration of those drugs decreased the damages for endothelium, such as vacuole formation and stripping off the basement membrane which were recognized by electron microscope. Based on these results, it was strongly suggested that initial damage of irradiated lungs might be induced by lipid peroxides and leukotrienes, and that Coenzyme Q10 and Azelastine could reduce radiation pneumonitis.

Topics: Animals; Coenzymes; Female; Lipid Peroxides; Lung; Mice; Phthalazines; Pneumonia; Pyridazines; Radiation Injuries, Experimental; Radiotherapy; Ubiquinone

Topics: Aged; Bronchial Diseases; Coenzymes; Female; Heart Diseases; Humans; Male; Middle Aged; Pneumonia; Ubiquinone

Three strains of Legionella feeleii from patients with pneumonia (425-MI-H, 691-WI-H, and 693-WI-H) and one environmental strain (713-MI-E) received at the Centers for Disease Control for reference diagnostic testing were compared with the type strain WO-44C-C3 (ATCC 35072) by DNA hybridization, chemical analysis of cellular fatty acids and ubiquinones, biochemical tests, and serological characteristics. All four isolates were assigned to the L. feeleii species on the basis of DNA hybridization results. However, strains 691-WI-H and 693-WI-H were serologically distinct from strain WO-44C-C3, as shown by their minimal reactivity (1 to 2+) with a direct immunofluorescence conjugate prepared against L. feeleii serogroup 1 (strain WO-44C-C3). Therefore, strains 691-WI-H and 693-WI-H were placed in a new L. feeleii serogroup (serogroup 2). The reference strain of L. feeleii serogroup 2 is 691-WI-H (ATCC 35849).

Topics: Animals; Antigens, Bacterial; Chick Embryo; DNA, Bacterial; Fatty Acids; Fluorescent Antibody Technique; Humans; Legionella; Legionnaires' Disease; Nucleic Acid Hybridization; Pneumonia; Rabbits; Serotyping; Ubiquinone