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Diet and lifestyle choices, notably the Western-type diet, are implicated in oxidative stress and inflammation, factors that elevate the risk of cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). In contrast, the Mediterranean of diet, rich in antioxidants, appears to have protective effects against these risks. This article highlights the dual role of diet in generating molecular hydrogen ( H 2 ) in the gut, and H 2 's subsequent influence on the pathophysiology and prevention of CVD and T2DM. Dietary fiber, flavonoids, and probiotics contribute to the production of liters of H 2 in the gut, functioning as antioxidants to neutralize free radicals and dampen inflammation. In the last two decades, mounting evidence has demonstrated that both endogenously produced and exogenously administered H 2 , whether via inhalation or H 2 -rich water (HRW), have potent anti-inflammatory effects across a wide range of biochemical and pathophysiological processes. Recent studies indicate that H 2 can neutralize hydroxyl and nitrosyl radicals, acting as a cellular antioxidant, thereby reducing oxidative stress and inflammation-leading to a significant decline in CVDs and metabolic diseases. Clinical and experimental research support the therapeutic potential of H 2 interventions such as HRW in managing CVDs and metabolic diseases. However, larger studies are necessary to verify the role of H 2 therapy in the management of these chronic diseases.
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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.
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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.
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COVID-19 , Ubiquinona , Humanos , Ubiquinona/uso terapéutico , Síndrome Post Agudo de COVID-19 , Sustancias Reactivas al Ácido Tiobarbitúrico , beta Caroteno , SARS-CoV-2 , Antioxidantes/uso terapéuticoRESUMEN
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.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Ubiquinona/farmacología , Antioxidantes/farmacología , Cisplatino/uso terapéutico , Cisplatino/farmacología , Sustancias Reactivas al Ácido Tiobarbitúrico , alfa-Tocoferol/farmacología , Estudios Prospectivos , Estrés Oxidativo , Triglicéridos/farmacología , HDL-ColesterolRESUMEN
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.
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Plaquetas/metabolismo , Metabolismo Energético , Mitocondrias/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Urotelio/patología , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Recuento de Células Sanguíneas , Estudios de Casos y Controles , Respiración de la Célula , Citrato (si)-Sintasa/metabolismo , Ácidos Grasos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
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.
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Hidrógeno/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ubiquinona/análogos & derivados , Animales , Antioxidantes/farmacología , Complejo I de Transporte de Electrón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Oxidación-Reducción/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/metabolismoRESUMEN
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.
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Plaquetas/citología , Mitocondrias/fisiología , Estaciones del Año , Ubiquinona/análogos & derivados , Antioxidantes/análisis , Plaquetas/metabolismo , Humanos , Ubiquinona/sangreRESUMEN
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.
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Antihipertensivos/uso terapéutico , Captopril/uso terapéutico , Hipertensión/tratamiento farmacológico , Luz , Melatonina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
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.
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COVID-19 , Humanos , Proyectos Piloto , Síndrome Post Agudo de COVID-19 , Mitocondrias , Metabolismo EnergéticoRESUMEN
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.
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COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Oxidación-Reducción , Mitocondrias , VacunaciónRESUMEN
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.
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Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Infusiones Intraventriculares , Ratas , Distribución Tisular , Ubiquinona/administración & dosificación , Regulación hacia Arriba/efectos de los fármacosRESUMEN
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.
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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.
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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.
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Artritis Reumatoide/diagnóstico , Biomarcadores/análisis , Plaquetas/patología , Respiración de la Célula , Mitocondrias/patología , Estrés Oxidativo , Ubiquinona/análogos & derivados , Adulto , Anciano , Artritis Reumatoide/metabolismo , Plaquetas/metabolismo , Estudios de Casos y Controles , Metabolismo Energético , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Proyectos Piloto , Ubiquinona/metabolismoRESUMEN
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.
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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.
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PURPOSE: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Pre-clinical and clinical studies have shown promising effects of H2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H2 per day) for 24 weeks. RESULTS: Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. CONCLUSION: Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.
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The neuropathological and clinical symptoms of Huntington's disease (HD) can be simulated in animal model with systemic administration of 3-nitropropionic acid (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme Q(10) (CoQ(10)), creatine, or nicotinamid. We studied the activity of creatine kinase (CK) and the function of mitochondrial respiratory chain in the brain of aged rats administered with 3-NP with and without previous application of antioxidants CoQ(10)+vitamin E. We used dynamic and steady-state methods of in vivo phosphorus magnetic resonance spectroscopy ((31)P MRS) for determination of the pseudo-first order rate constant (k(for)) of the forward CK reaction, the phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pH(i) and Mg(i)(2+) content in the brain. The respiratory chain function of isolated mitochondria was assessed polarographically; the concentration of CoQ(10) and alpha-tocopherol by HPLC. We found significant elevation of k(for) in brains of 3-NP rats, reflecting increased rate of CK reaction in cytosol. The function of respiratory chain in the presence of succinate was severely diminished. The activity of cytochromeoxidase and mitochondrial concentration of CoQ(10) was unaltered; tissue content of CoQ(10) was decreased in 3-NP rats. Antioxidants CoQ(10)+vitamin E prevented increase of k(for) and the decrease of CoQ(10) content in brain tissue, but were ineffective to prevent the decline of respiratory chain function. We suppose that increased activity of CK system could be compensatory to decreased mitochondrial ATP production, and CoQ(10)+vitamin E could prevent the increase of k(for) after 3-NP treatment likely by activity of CoQ(10) outside the mitochondria. Results of our experiments contributed to elucidation of mechanism of beneficial effect of CoQ(10) administration in HD and showed that the rate constant of CK is a sensitive indicator of brain energy disorder reflecting therapeutic effect of drugs that could be used as a new in vivo biomarker of neurodegenerative diseases.
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Encéfalo/metabolismo , Modelos Animales de Enfermedad , Enfermedad de Huntington/metabolismo , Ubiquinona/análogos & derivados , Vitamina E/farmacología , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/enzimología , Coenzimas , Creatina Quinasa/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Masculino , Fosforilación Oxidativa , Fosfocreatina/metabolismo , Ratas , Ratas Wistar , Ubiquinona/farmacologíaRESUMEN
UNLABELLED: Bronchial asthma is a chronic inflammatory disease of respiratory system, with disturbances in the dynamic balance of oxidant-antioxidant capacity of the lungs. Long-term administration of corticosteroids has been shown to result in mitochondrial dysfunction and oxidative damage of mitochondrial and nuclear DNAs. We previously documented decreased coenzyme Q(10) (CoQ(10)) and alpha-tocopherol concentrations in plasma and blood in corticosteroid-dependent bronchial asthma patients. In the present study we demonstrate that CoQ(10) supplementation reduces the dosage of corticosteroids in these patients. PATIENTS AND METHODS: This was an open, cross-over, randomized clinical study with 41 bronchial asthma patients (13 males, 28 females), ages 25-50 years. All patients suffered from persistent mild to moderate asthma. The patients were divided into two groups, one group receiving standard antiasthmatic therapy and clinically stabilized, and the second group receiving, in addition, antioxidants consisting of CoQ(10) as Q-Gel (120 mg) + 400 mg alpha-tocopherol + 250 mg vitamin C a day. The groups were crossed over at 16 weeks for a total duration of 32 weeks. RESULTS AND CONCLUSIONS: Data show that patients with corticosteroid-dependent bronchial asthma have low plasma CoQ(10) concentrations that may contribute to their antioxidant imbalance and oxidative stress. A reduction in the dosage of corticosteroids required by the patients following antioxidant supplementation was observed, indicating lower incidence of potential adverse effects of the drugs, decreased oxidative stress. This study also demonstrates the significant uptake of CoQ(10) by lung tissue in a rat model using hydrosoluble CoQ(10) (Q-Gel).
Asunto(s)
Corticoesteroides/administración & dosificación , Asma/tratamiento farmacológico , Ubiquinona/análogos & derivados , Adulto , Animales , Ácido Ascórbico/uso terapéutico , Coenzimas , Estudios Cruzados , Femenino , Humanos , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Ratas , Ratas Wistar , Ubiquinona/sangre , Ubiquinona/uso terapéutico , alfa-Tocoferol/uso terapéuticoRESUMEN
Creatine kinase (CK) plays a central role in energy transfer in cells with high-energy demands, and the enzyme is rather susceptible to oxidative inactivation. The aim of the present study was to investigate whether the rate constant of forward CK reaction (k(for)) is a suitable indicator of alterations in cerebral energy metabolism. We monitored k(for) in the rat brain non-invasively by in vivo phosphorus ((31)P) magnetic resonance spectroscopy (MRS). To alter energy metabolism, we applied following experimental models: Huntington's disease, diabetes mellitus, chronic alcohol intoxication and chronic cerebral hypoperfusion (vascular dementia model). Results of our (31)P MRS experiment confirm importance of creatine kinase/phosphocreatinine (CK/PCr) system in the regulation of brain energy metabolism in vivo because a kinetic parameter k(for) was significantly changed in all above animal models that simulate neurodegenerative diseases or commonly during oxidative stress. Using this method we distinguished vascular dementia (VD) and Huntington disease (HD), because in VD model a kinetic parameter k(for) decreased and in the case HD increased. Considering the importance of CK for the maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity in the brain may be one of the mechanisms by which various neurodegenerative diseases might be monitored just by means saturation transfer method (31)P MRS.