Active hydrogen inhalation (H(H₂O)_m) has powerful antioxidant and antiapoptotic effects. In recent years, it has been used in a number of experimental and clinical studies.Aim. To study the safety and effectiveness of inhalation of the “active form of hydrogen” (AFV;(H(H₂O)_m)) in the rehabilitation program of coronavirus disease 2019 (COVID-19) survivors during the recovery period.Material and methods. This randomized controlled parallel prospective study included 60 COVID-19 survivors with post-COVID-19 syndrome (ICD-10: U09.9) during the recovery period, with clinical manifestations of chronic fatigue syndrome (CFS), who received standard therapy in accordance with the management protocol of patients with CFS (ICD-10: G93.3): physiotherapy and medication therapy with drugs containing magnesium, B vitamins and L-carnitine. The patients were divided into 2 groups. The experimental group (n=30) included patients who received hydrogen inhalation for 90 minutes every day during 10 days (SUISONIA hydrogen inhalation device, Japan). The control group (n=30) consisted of patients who received standard therapy. In both groups, patients were comparable in sex and mean age: in the experimental group — 53 (22; 70) years, in the control group — 51 (25; 70) years. Biological markers of systemic inflammation, oxygen transport, lactate metabolism, intrapulmonary shunting, 6-minute walk test, and vascular endothelial function were determined in all patients on the 1^st and 10^th days of follow-up.Results. In the experimental group, a decrease in following parameters was revealed: stiffness index (SI), from 8,8±1,8 to 6,8±1,5 (p<0,0001); ALT, from 24,0±12,7 to 20,22±10,61 U/L (p<0,001); venous blood lactate, from 2,5±0,8 to 1,5±1,0 mmol/L (p<0,001); capillary blood lactate, from 2,9±0,8 to 2,0±0,8 mmol/L (p<0,0001); estimated pulmonary shunt fraction (Qs/Qt, Berggren equation, 1942) from 8,98±5,7 to 5,34±3,2 (p<0,01); white blood cells, from 6,64±1,57 to 5,92±1,32 109/L. In addition, we revealed an increase in the refractive index (RI) from 46,67±13,26% to 63,32±13,44% (p<0,0001), minimum blood oxygen saturation (SpO₂) from 92,25±2,9 to 94,25±1, 56% (p<0,05), direct bilirubin from 2,99±1,41 to 3,39±1,34 pmol/L (p<0,01), partial oxygen tension (PvO₂) from 26,9±5,0 to 34,8±5,6 mm Hg (p<0,0001), venous oxygen saturation (SvO2) from 51,8±020,6 to 61,1±018,1% (p<0,05), partial capillary oxygen tension (PcO₂) from 48,7±15,4 to 63,8±21,2 mm Hg (p<0,01), capillary oxygen saturation (ScO₂) from 82,2±4,2 to 86,2±4,8% (p<0,01), distance in 6 minute walk test from 429±45,0 to 569±60 m.Conclusion. Inhalation therapy with H(H₂O)m in the rehabilitation program of COVID-19 survivors during the recovery period is a safe and highly effective method. Manifestations of silent hypoxemia and endothelial dysfunction decreased, while exercise tolerance increased. As for laboratory tests, a decrease in the white blood cell count, estimated pulmonary shunt fraction and lactate content parameters was revealed.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2–3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child–Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2–3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male Wistar rats were subcutaneously injected with a water–alcohol solution of monocrotaline or a control with an only water–alcohol solution. One group of monocrotaline-injected animals was placed in a plastic box that was constantly ventilated with atmospheric air containing 4% of molecular hydrogen, and the two groups of rats, injected with monocrotaline or vehicle, were placed in boxes ventilated with atmospheric air. After 21 days, hemodynamic parameters were measured under urethane narcosis. The results showed that, although hydrogen inhalation had no effect on the main markers of pulmonary hypertension induced by monocrotaline injection, there was a reduction in systemic blood pressure due to its systolic component, and a decrease in TGF-β expression, as well as a reduction in tryptase-containing mast cells.

Ubiquinol exhibits anti-inflammatory and antioxidant properties. Selenium is a part of a number of antioxidant enzymes. The monocrotaline inducible model of pulmonary hypertension used in this study includes pathological links that may act as an application for the use of ubiquinol with high bioavailability and selenium metabolic products. On day 1, male and female rats were subcutaneously injected with a water-alcohol solution of monocrotaline or only water-alcohol solution. On days 7 and 14, some animals were intravenously injected with either ubiquinol’s vehicle or solubilized ubiquinol, or orally with selenium powder daily, starting from day 7, or received both ubiquinol + selenium. Magnetic resonance imaging of the lungs was performed on day 20. Hemodynamic parameters and morphometry were measured on day 22. An increased right ventricle systolic pressure in relation to control was demonstrated in all groups of animals of both sexes, except the group of males receiving the combination of ubiquinol + selenium. The relative mass of the right ventricle did not differ from the control in all groups of males and females receiving either ubiquinol alone or the combination. Magnetic resonance imaging revealed impaired perfusion in almost all animals examined, but pulmonary fibrosis developed in only half of the animals in the ubiquinol group. Intravenous administration of ubiquinol has a protective effect on monocrotaline-induced pulmonary hypertension development resulting in reduced right ventricle hypertrophy, and lung mass. Ubiquinol + selenium administration resulted in a less severe increase in the right ventricle systolic pressure in male rats but not in females 3 weeks after the start of the experiment. This sex-dependent effect was not observed in the influence of ubiquinol alone.

Selenium is an important micronutrient that is essential for the functioning of the human body. Being a component of the active center of several antioxidant enzymes selenium prevents cell injury by free radicals. Decline in selenium-containing enzymes results in progression of oxidative stress and chronic inflammation, which are considered as possible causes for the development of many cardiovascular diseases. This review focuses on mechanisms for prevention of myocardial and vascular injury through the adequate selenium supply to the body. The importance of monitoring and correction of the selenium status in appropriate patients is underlined.

Hydrogen is known to have selective antioxidant properties. It binds highly reactive hydroxyl radicals. The pathogenesis of the monocrotaline animal model of pulmonary hypertension is associated with oxidative stress and leads to all the symptoms of pulmonary hypertension (PH) and interstitial lung disease (ILD) associated with hypertension.The aim of this work was to study the effect of 4% hydrogen inhalations on the symptoms of PH and ILD in rats.Methods. To model monocrotaline-induced pulmonary hypertension (MCT-PH), two groups of animals received a single subcutaneous injection of monocrotaline (MCT) on day 1. The control group was injected subcutaneously with MCT solvent only. The animals receiving MCT were further divided into 2 subgroups. Subgroup 1 rats breathed room air and subgroup 2 rats breathed a mixture of room air and 4% hydrogen. The regular inhalations continued until day 21. On day 21, hemodynamic parameters were measured under urethane anesthesia, the heart and its components and the lungs were weighed, and lung tissue was preserved for morphological study.Results. The inhalation had no effect on the main cardiovascular symptoms of PH, but a positive effect on the state of the connective tissue of the lungs affected by PH was shown. The mast cell response was reduced both quantitatively and functionally. There was a decrease in tryptase expression by mast cells, with predominance of the forms without signs of degranulation. TGF-β secretion was also significantly reduced and visualized by immunopositive cells in alveolar cellular structures and vessel walls.Conclusion. Inhalation of 4% hydrogen reduces inflammation and fibrosis of lung tissue during the development of MCT-PH.