ABSTRACT
Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.
ABSTRACT
BACKGROUND: SARS-CoV-2 infection is associated with inflammation, decrease in antioxidants and oxidative damage. We aimed to investigate whether ubiquinol, reduced form of coenzyme Q10 (CoQ10), with mountain spa rehabilitation (MR) will contribute to recovering of patients with post-COVID-19 syndrome. METHODS: The study included 36 patients on MR lasting 16-18 days. Twentytwo patients were supplemented with ubiquinol 2x100 mg/day (MRQ), 14 underwent MR without supplementation. The control group consisted of 15 healthy volunteers. Concentrations of total CoQ10 (ubiquinone + ubiquinol), α- and γ-tocopherol were determined in platelets (PLT), in blood and plasma, also ß-carotene was determined. Plasma concentration of thiobarbituric acidreactive substances (TBARS) was used as the oxidative stress marker. Clinical symptoms were evaluated by questionnaire. RESULTS: MRQ group showed a significant increase in CoQ10, namely in PLT by 68 %, in blood by 194 %, and in plasma by 232 %. In MR group, CoQ10 stayed unchanged. In both groups, the initially increased concentrations of tocopherols in PLT returned nearly to the control values. ß-carotene levels decreased in both groups while TBARS decreased slightly in the MRQ group. More clinical symptoms disappeared in the MRQ group. CONCLUSION: Accelerated recovery of patients with post-COVID-19 syndrome was proven after mountain spa rehabilitation and ubiquinol supplementation. Increased systemic and cellular CoQ10 concentration alleviated clinical symptoms and improved antioxidant protection of the patients. We draw attention to the importance of monitoring and ensuring adequate levels of CoQ10 in post-COVID-19 syndrome (Tab. 2, Fig. 1, Ref. 45). Text in PDF www.elis.sk Keywords: COVID-19, mountain spa rehabilitation, ubiquinol, coenzyme Q10, vitamins, TBARS.
Subject(s)
COVID-19 , Ubiquinone , Humans , Ubiquinone/therapeutic use , Post-Acute COVID-19 Syndrome , Thiobarbituric Acid Reactive Substances , beta Carotene , SARS-CoV-2 , Antioxidants/therapeutic useABSTRACT
Oxidative stress plays an important role in cancer pathogenesis, and thiobarbituric acid-reactive substance level (TBARS)a parameter of lipid peroxidationhas prognostic significance in chemotherapy-naive patients with metastatic urothelial carcinoma (mUC). However, the effect of cisplatin (CDDP)-based chemotherapy on oxidative stress, coenzyme Q10, and antioxidants remains unknown. The objective of this prospective study was to determine possible changes in the CoQ10 (coenzyme Q10)/lipids ratio, antioxidants (α-tocopherol, γ-tocopherol, ß-carotene, CoQ10), total antioxidant status (TAS), and TBARS in plasma at baseline and during first-line chemotherapy based on CDDP in mUC subjects. In this prospective study, 63 consecutive patients were enrolled. The median age was 66 years (range 39−84), performance status according to the Eastern Cooperative Oncology Group (ECOG) was 2 in 7 subjects (11.1%), and visceral metastases were present in 31 (49.2%) patients. Plasma antioxidants were determined by HPLC and TAS and TBARS spectrophotometrically. After two courses of chemotherapy, we recorded significant enhancements compared to baseline for total cholesterol (p < 0.0216), very low-density lipoprotein (VLDL) cholesterol (p < 0.002), triacylglycerols (p < 0.0083), α-tocopherol (p < 0.0044), and coenzyme Q10-TOTAL (p < 0.0001). Ratios of CoQ10/total cholesterol, CoQ10/HDL-cholesterol, and CoQ10/LDL-cholesterol increased during chemotherapy vs. baseline (p < 0.0048, p < 0.0101, p < 0.0032, respectively), while plasma TBARS declined (p < 0.0004). The stimulation of antioxidants could be part of the defense mechanism during CDDP treatment. The increased index of CoQ10-TOTAL/lipids could reflect the effect of CDDP protecting lipoproteins from peroxidation.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Ubiquinone/pharmacology , Antioxidants/pharmacology , Cisplatin/therapeutic use , Cisplatin/pharmacology , Thiobarbituric Acid Reactive Substances , alpha-Tocopherol/pharmacology , Prospective Studies , Oxidative Stress , Triglycerides/pharmacology , Cholesterol, HDLABSTRACT
Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q10 (CoQ10) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and ß-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ10 level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ10 cycle (Q-junction) to CI.
Subject(s)
Blood Platelets/metabolism , Energy Metabolism , Mitochondria/metabolism , Urinary Bladder Neoplasms/metabolism , Urothelium/pathology , Adult , Aged , Aged, 80 and over , Antioxidants/metabolism , Blood Cell Count , Case-Control Studies , Cell Respiration , Citrate (si)-Synthase/metabolism , Fatty Acids/metabolism , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Mitochondria are the major source of cellular energy metabolism. In the cardiac cells, mitochondria produce by way of the oxidative phosphorylation more than 90% of the energy supply in the form of ATP, which is utilized in many ATP-dependent processes, like cycling of the contractile proteins or maintaining ion gradients. Reactive oxygen species (ROS) are by-products of cellular metabolism and their levels are controlled by intracellular antioxidant systems. Imbalance between ROS and the antioxidant defense leads to oxidative stress and oxidative changes to cellular biomolecules. Molecular hydrogen (H2) has been proved as beneficial in the prevention and therapy of various diseases including cardiovascular disorders. It selectively scavenges hydroxyl radical and peroxynitrite, reduces oxidative stress, and has anti-inflammatory and anti-apoptotic effects. The effect of H2 on the myocardial mitochondrial function and coenzyme Q levels is not well known. In this paper, we demonstrated that consumption of H2-rich water (HRW) resulted in stimulated rat cardiac mitochondrial electron respiratory chain function and increased levels of ATP production by Complex I and Complex II substrates. Similarly, coenzyme Q9 levels in the rat plasma, myocardial tissue, and mitochondria were increased and malondialdehyde level in plasma was reduced after HRW administration. Based on obtained data, we hypothesize a new metabolic pathway of the H2 effect in mitochondria on the Q-cycle and in mitochondrial respiratory chain function. The Q-cycle contains three coenzyme Q forms: coenzyme Q in oxidized form (ubiquinone), radical form (semiquinone), or reduced form (ubiquinol). H2 may be a donor of both electron and proton in the Q-cycle and thus we can suppose stimulation of coenzyme Q production. When ubiquinone is reduced to ubiquinol, lipid peroxidation is reduced. Increased CoQ9 concentration can stimulate electron transport from Complex I and Complex II to Complex III and increase ATP production via mitochondrial oxidative phosphorylation. Our results indicate that H2 may function to prevent/treat disease states with disrupted myocardial mitochondrial function.
Subject(s)
Hydrogen/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Ubiquinone/analogs & derivatives , Animals , Antioxidants/pharmacology , Electron Transport Complex I/metabolism , Lipid Peroxidation/drug effects , Male , Oxidation-Reduction/drug effects , Oxidative Phosphorylation/drug effects , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Ubiquinone/metabolismABSTRACT
The rooibos tea (RT) is a source of valuable dietary dihydrochalcones ï aspalathin, and nothofagin and other polyphenols. Many in vitro and in vivo studies have shown that RT flavonoids have strong antioxidant effect and significantly reduce oxidative stress. We investigated the antioxidant activity and protective effect of an aqueous extract of RT on the liver mitochondria oxidative phosphorylation in rats with carbon tetrachloride-induced (CCl4-induced) liver damage. Mitochondrial respiration and ATP production was determined amperometrically using a Clark-type oxygen electrode. We found significantly decreased parameters of oxidative phosphorylation in the group having received CCl4 for 10 weeks. Simultaneous administration of RT increased oxygen uptake stimulated with ADP, and the rate of ATP generation in the mitochondria of rats, both having been impaired in rats treated with CCl4 only. Treatment with RT significantly decreased CCl4-induced elevated enzyme levels, improved capacity of the respiratory chain and energy production, presumably due to its potent and direct antioxidant activity, including inhibition of mitochondrial lipid peroxidation. Improved histological features support the view of antioxidant and membrane-stabilizing activity of RT. This fact may play a significant role in the protection of the liver from injury caused by known toxins, and from subsequent development of steatosis and fibrosis..
Subject(s)
Aspalathus/chemistry , Cell Respiration/drug effects , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Energy Metabolism/drug effects , Liver/drug effects , Plant Extracts/pharmacology , Tea/chemistry , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/prevention & control , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Mitochondria, Liver/pathology , Oxidative Phosphorylation/drug effects , Plant Extracts/chemistry , RatsABSTRACT
Seasonal variations in temperature may influence the physiological and pathological metabolic pathways, concentrations of antioxidants, degree of oxidative stress and mitochondrial function. The aim of this study was to evaluate platelet mitochondrial function in human subjects during seasonal variations in temperature. Two groups of healthy young subjects were enroled in the study. Winter group, mean outside temperature was 4.77°C and Spring group, mean outside temperature was 24.32°C. High-resolution respirometry method was used for determination of mitochondrial respiration and oxidative phosphorylation in platelets. Concentrations of coenzyme Q10 (CoQ10) and tocopherols were determined in platelets, blood and plasma. Our data showed slightly (not significantly) reduced respiration in intact platelets, basal and ADP-stimulated mitochondrial respiration at Complex I, as well as CoQ10-TOTAL and α-tocopherol concentrations in winter. The concentration of γ-tocopherol was higher in winter. Platelet mitochondrial ATP production depended on platelet CoQ10-TOTAL concentration in winter, not in spring. We conclude that seasonal temperature participates in the mechanism of platelet mitochondrial respiratory chain function and oxidative phosphorylation that depends on their CoQ10-TOTAL concentration at lower winter outside temperature. CoQ10 supplementation may improve platelets mitochondrial ATP production at winter season. High-resolution respirometry offers sensitive method for detection of changes of platelets mitochondrial respiratory function.
Subject(s)
Blood Platelets/cytology , Mitochondria/physiology , Seasons , Ubiquinone/analogs & derivatives , Antioxidants/analysis , Blood Platelets/metabolism , Humans , Ubiquinone/bloodABSTRACT
Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.
Subject(s)
Antihypertensive Agents/therapeutic use , Captopril/therapeutic use , Hypertension/drug therapy , Light , Melatonin/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Blood Pressure/drug effects , Male , Oxidative Stress/drug effects , Rats , Rats, WistarABSTRACT
European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR - mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16-18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome.
Subject(s)
COVID-19 , Humans , Pilot Projects , Post-Acute COVID-19 Syndrome , Mitochondria , Energy MetabolismABSTRACT
BACKGROUND: Mitochondrial dysfunction and redox cellular imbalance indicate crucial function in COVID-19 pathogenesis. Since 11 March 2020, a global pandemic, health crisis and economic disruption has been caused by SARS-CoV-2 virus. Vaccination is considered one of the most effective strategies for preventing viral infection. We tested the hypothesis that preventive vaccination affects the reduced bioenergetics of platelet mitochondria and the biosynthesis of endogenous coenzyme Q10 (CoQ10) in patients with post-acute COVID-19. MATERIAL AND METHODS: 10 vaccinated patients with post-acute COVID-19 (V + PAC19) and 10 unvaccinated patients with post-acute COVID-19 (PAC19) were included in the study. The control group (C) consisted of 16 healthy volunteers. Platelet mitochondrial bioenergy function was determined with HRR method. CoQ10, γ-tocopherol, α-tocopherol and ß-carotene were determined by HPLC, TBARS (thiobarbituric acid reactive substances) were determined spectrophotometrically. RESULTS: Vaccination protected platelet mitochondrial bioenergy function but not endogenous CoQ10 levels, in patients with post-acute COVID-19. CONCLUSIONS: Vaccination against SARS-CoV-2 virus infection prevented the reduction of platelet mitochondrial respiration and energy production. The mechanism of suppression of CoQ10 levels by SARS-CoV-2 virus is not fully known. Methods for the determination of CoQ10 and HRR can be used for monitoring of mitochondrial bioenergetics and targeted therapy of patients with post-acute COVID-19.
Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Oxidation-Reduction , Mitochondria , VaccinationABSTRACT
Brain coenzyme Q10 (CoQ10) concentration can influence the activity of several brain regions, including those which participate in the regulation of cardiovascular circadian rhythms, food intake, neuroendocrine stress response, activity and sleep regulation. However, the effect of supplemented ubiquinol (reduced CoQ) into brain regions is not known. This study determined baseline levels of ubiquinone (oxidized CoQ) in various rat brain regions and proved the bioavailability of the liposomal ubiquinol to selected brain regions after its administration into right brain ventricle. Our data indicate that administration of ubiquinol may create the basis for modulation of neuronal activities in specific brain regions.
Subject(s)
Brain/drug effects , Brain/metabolism , Ubiquinone/analogs & derivatives , Ubiquinone/metabolism , Animals , Dose-Response Relationship, Drug , Infusions, Intraventricular , Rats , Tissue Distribution , Ubiquinone/administration & dosage , Up-Regulation/drug effectsABSTRACT
Chronic D-galactose administration induces accelerated aging in rodents. The aim of the study was to find by in vivo31P MRS suitable markers of early stages of brain degeneration on this metabolic model in rats. Additionally, we studied the therapeutic effect of antidiabetic drug metformin. The study has been extended by in vitro determination of mitochondrial function in brain, skeletal muscle and liver mitochondria, oxidative stress parameter thiobarbituric acid reactive substances (TBARS), and lipophilic antioxidants levels. In vivo31P MRS revealed lower intracellular pH (pHi) and lower inorganic phosphate to ATP ratio (Pi/ATP), with higher index of oxidative phosphorylation - phosphocreatine (PCr) to Pi ratio - in brain of rats chronically administered with D-galactose. The function of brain mitochondria was not affected. Administration of metformin diminished changes in brain pHi and plasma TBARS. The function of skeletal muscle mitochondria and their coenzyme Q (CoQ) content were considerably reduced after D-galactose administration. Metformin administered simultaneously with D-galactose did not prevent these changes. The results of in vivo31P MRS revealed evidence of early stage of neurodegeneration that may indicate pre-inflammation. Our data show different susceptibility of brain, skeletal muscle, and liver to the chronic exposure to D-galactose and metformin. The D-galactose model presented in the literature as a model for "age-related dementia" had much more devastating effects on skeletal muscle than on the brain.
Subject(s)
Galactose , Metformin , Adenosine Triphosphate/metabolism , Aging/metabolism , Animals , Brain/metabolism , Energy Metabolism , Galactose/pharmacology , Liver/metabolism , Metformin/pharmacology , Muscle, Skeletal/metabolism , Oxidative Stress , Rats , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
European Association of Spa Rehabilitation recommend spa rehabilitation for patients with post COVID-19 syndrome (post C-19). We studied effects of special mountain spa rehabilitation program and its combination with ubiquinol (reduced form of coenzyme Q10-CoQ10) supplementation on pulmonary function, clinical symptoms, endogenous CoQ10 levels, and platelet mitochondrial bioenergetics of patients with post C-19. 36 patients with post C-19 enrolled for rehabilitation in mountain spa resort and 15 healthy volunteers representing the control group were included in this study. 14 patients with post C-19 (MR group) were on mountain spa rehabilitation lasting 16-18 days, 22 patients (MRQ group) were supplemented with ubiquinol (2 × 100 mg/day) during the rehabilitation and additional 12-14 days at home. Clinical symptoms and functional capacity of the lungs were determined in the patients before and after the spa rehabilitation program. Platelet bioenergetics by high-resolution respirometry, plasma TBARS concentration, and CoQ10 concentration in blood, plasma and platelets were evaluated before and after the spa rehabilitation program, and in 8 patients of MRQ group also after additional 12-14 days of CoQ10 supplementation. Pulmonary function and clinical symptoms improved after the rehabilitation program in both groups, 51.8% of symptoms disappeared in the MR group and 62.8% in the MRQ group. Platelet mitochondrial Complex I (CI)-linked oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity were markedly reduced in both groups of patients. After the rehabilitation program the improvement of these parameters was significant in the MRQ group and moderate in the MR group. CI-linked OXPHOS and ET capacity increased further after additional 12-14 days of CoQ10 supplementation. CoQ10 concentration in platelets, blood and plasma markedly raised after the spa rehabilitation with ubiquinol supplementation, not in non-supplemented group. In the MRQ group all parameters of platelet mitochondrial respiration correlated with CoQ10 concentration in platelets, and the increase in CI-linked OXPHOS and ET capacity correlated with the increase of CoQ10 concentration in platelets. Our data show a significant role of supplemented ubiquinol in accelerating the recovery of mitochondrial health in patients with post C-19. Mountain spa rehabilitation with coenzyme Q10 supplementation could be recommended to patients with post C-19. This study was registered as a clinical trial: ClinicalTrials.gov ID: NCT05178225.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2'-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.
ABSTRACT
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimunne disorder affecting both small and large synovial joints, leading to their destruction. Platelet biomarkers are involved in inflammation in RA patients. Increased circulating platelet counts in RA patients may contribute to platelet hyperactivity and thrombosis. In this pilot study we evaluated platelet mitochondrial bioenergy function, CoQ10 levels and oxidative stress in RA patients. METHODS: Twenty-one RA patients and 19 healthy volunteers participated in the study. High resolution respirometry (HRR) was used for analysis of platelet mitochondrial bioenergetics. CoQ10 was determined by HPLC method; TBARS were detected spectrophotometrically. RESULTS: Slight dysfunction in platelet mitochondrial respiration and reduced platelet CoQ10 levels were observed in RA patients compared with normal controls. CONCLUSIONS: The observed decrease in platelet CoQ10 levels may lead to platelet mitochondrial dysfunction in RA diseases. Determination of platelet mitochondrial function and platelet CoQ10 levels could be used as new diagnostic strategies for mitochondrial bioenergetics in rheumatoid diseases.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Biomarkers/analysis , Blood Platelets/pathology , Cell Respiration , Mitochondria/pathology , Oxidative Stress , Ubiquinone/analogs & derivatives , Adult , Aged , Arthritis, Rheumatoid/metabolism , Blood Platelets/metabolism , Case-Control Studies , Energy Metabolism , Female , Humans , Male , Middle Aged , Mitochondria/metabolism , Pilot Projects , Ubiquinone/metabolismABSTRACT
Oxidative stress plays a significant role in development and progression of cancer, including urothelial carcinomas. TBARS (Thiobarbituric acid reactive substances) represents a marker of oxidative stress increased in various diseases. In this prospective study, we tested the hypothesis of plasma TBARS concentration and correlation with survival in chemotherapy naïve MUC (metastatic urothelial carcinoma) patients. Most of subjects (Nâ¯=â¯65) were treated with gemcitabine and cisplatin (GC) chemotherapy. Performance status ECOG ≥2 had 11 patients, visceral metastases were present in 43. Based upon the mean of plasma TBARS, subjects were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared by log-rank test. At median follow-up of 9.6â¯months, 65 patients experienced progression and 64 died. Subjects with low TBARS had significantly better PFS (HR 0.51) and OS (HR 0.44) opposed to high TBARS. Patients with low TBARS had significantly higher rate of neutropenia G4 and less liver involvement. High TBARS correlated with BMI above 30â¯kg/m2. Performance status and plasma TBARS were proven to be independent predictors of PFS and OS. In this study, high TBARS in MUC patients were associated with poor survival, likely due to more aggressive disease activity as reflected in increased liver involvement. Therefore, this biomarker could be used in clinical practice for early identification of patients with worse prognosis, better patient stratification, and treatment decision making.
ABSTRACT
Brain energy disorders can be present in aged men and animals. To this respect, the mitochondrial and free radical theory of aging postulates that age-associated brain energy disorders are caused by an imbalance between pro- and anti-oxidants that can result in oxidative stress. Our study was designed to investigate brain energy metabolism and the activity of endogenous antioxidants during their lifespan in male Wistar rats. In vivo brain bioenergetics were measured using ³¹P nuclear magnetic resonance (NMR) spectroscopy and in vitro by polarographic analysis of mitochondrial oxidative phosphorylation. When compared to the young controls, a significant decrease of age-dependent mitochondrial respiration and adenosine-3-phosphate (ATP) production measured in vitro correlated with significant reduction of forward creatine kinase reaction (kfor) and with an increase in phosphocreatine (PCr)/ATP, PCr/Pi and PME/ATP ratio measured in vivo. The levels of enzymatic antioxidants catalase, GPx and GST significantly decreased in the brain tissue as well as in the peripheral blood of aged rats. We suppose that mitochondrial dysfunction and oxidative inactivation of endogenous enzymes may participate in age-related disorders of brain energy metabolism.
Subject(s)
Aging/physiology , Brain/metabolism , Energy Metabolism , Adenosine Triphosphate/metabolism , Animals , Antioxidants/metabolism , Magnetic Resonance Spectroscopy , Male , Mitochondria/metabolism , Oxidation-Reduction , Oxidative Phosphorylation , Rats , Rats, WistarABSTRACT
Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and a decrease of glomerular filtration rate. Reduced mitochondrial function, coenzyme Q10 (CoQ10), and increased oxidative stress in patients with CKD contribute to the disease progression. We tested whether CoQ10 levels, oxidative stress and platelet mitochondrial bioenergetic function differ between groups of CKD patients. METHODS: Twenty-seven CKD patients were enrolled in this trial, 17 patients had arterial hypertension (AH) and 10 patients had arterial hypertension and diabetes mellitus (AH and DM). The control group consisted of 12 volunteers. A high-resolution respirometry (HRR) method was used for the analysis of mitochondrial bioenergetics in platelets, and an HPLC method with UV detection was used for CoQ10 determination in platelets, blood, and plasma. Oxidative stress was determined as thiobarbituric acid reactive substances (TBARS). RESULTS: Platelets mitochondrial respiration showed slight, not significant differences between the groups of CKD patients and control subjects. The oxygen consumption by intact platelets positively correlated with the concentration of CoQ10 in the platelets of CKD patients. CONCLUSION: A decreased concentration of CoQ10 and oxidative stress could contribute to the progression of renal dysfunction in CKD patients. The parameters of platelet respiration assessed by high-resolution respirometry can be used only as a weak biological marker for mitochondrial diagnosis and therapy monitoring in CKD patients.
ABSTRACT
Diabetes-induced injury related to hyperglycaemia is associated with impaired function of mitochondria. Regardless of their cytotoxicity, PAMAM [poly(amido)amine] G4 dendrimers lower plasma glucose and suppress long-term markers of diabetic hyperglycaemia in experimental diabetes. In the present study, we aimed at verifying whether such modulatory effects of PAMAM G4 (0.5 micromol/kg of body weight daily for 60 days) may contribute to improved respiration in heart and liver mitochondria from streptozotocin-diabetic rats. PAMAM G4 alleviated long-term markers of hyperglycaemia and reduced blood and tissue lipophilic antioxidants in diabetic animals, but did not restore mitochondrial function. In hearts, but not livers, dendrimers further reduced respiratory function and oxidative phosphorylation. Thus ameliorating effects of PAMAM G4 on glycation and glycoxidation in experimental diabetes are not sufficient to restore the impaired mitochondrial function in diabetes.
Subject(s)
Dendrimers/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Mitochondria, Heart/drug effects , Mitochondria, Liver/drug effects , Animals , Antioxidants/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/chemically induced , Disease Models, Animal , Male , Mitochondria, Heart/metabolism , Mitochondria, Liver/metabolism , Nylons , Oxidative Phosphorylation , Rats , Rats, Wistar , Tocopherols/pharmacology , Ubiquinone/pharmacologyABSTRACT
The effect of simvastatin administered for 10 days on coenzyme Q and antioxidant/oxidant balance in a rat model of diabetes mellitus and hypercholesterolaemia was studied. In the diabetic-hypercholesterolaemic rats the signs of oxidative stress-decreased alpha-tocopherol/cholesterol in the plasma (p < 0.01) and alpha-tocopherol in liver (p < 0.001) together with increased lipid peroxidation in the liver (TBARS, p < 0.05) were found. Increased coenzyme Q9 concentrations in the plasma (p < 0.05) and liver (p < 0.01), coenzyme Q10 in the myocardium (p < 0.05) and in the liver (p < 0.01) may indicate adaptation to oxidative stress. Administration of simvastatin (10 mg/kg) to the diabetic-hypercholesterolaemic rats counteracted increased myocardial (coenzyme Q10, p < 0.05) and liver (total coenzyme Q9, p < 0.05) coenzyme Q concentrations but did not improve alpha-tocopherol depletion and increased formation of TBARS in the liver. Even though simvastatin treatment did not induce coenzyme Q deficiency in plasma, heart and liver of the diabetic-hypercholesterolaemic rats as compared to the control levels, it was not able to prevent completely the changes in antioxidant/oxidant balance induced by diabetes and hypercholesterolaemia. The results highlight the importance of studying the effect of statins on the coenzyme Q levels in the animal models of pathological conditions known to change the initial antioxidant defence system.