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The liver is the main organ responsible for the metabolism of different substances. At the same time it is the primary target organ for many toxic chemicals, which are metabolized there. Carbon tetrachloride is a wellknown hepatotoxin widely used to induce acute toxic liver injury in a wide range of laboratory animals. This substance induces oxidative damage, inflammation and fibrosis in the liver. AIM: The aim is to evaluate the peculiarities of nitrogen metabolism in rats on the background of acute toxic hepatitis and its correction with L-arginin and L-ornitin. MATERIALS AND METHODS: The study was performed on 40 outbred white male rats with experimental hepatitis, caused by carbon tetrachloride. The animals were divided into five groups: control group (the rats were simulated carbon tetrachloride poisoning and its correction by administering of olive oil and normal saline in equivalent doses), acute carbon tetrachloride hepatitis (single intraperitoneal injection of 50% carbon tetrachloride oil solution at the dose of 2 ml/kg-1 of body weight and simulation of treatment by administration of normal saline in equivalent doses), acute carbon tetrachloride hepatitis + L-ornithine (1000 mg×kg-1), acute carbon tetrachloride hepatitis + L-arginine (500 mg×kg-1) and acute carbon tetrachloride hepatitis + combination of substances. RESULTS: On the background of acute carbon tetrachloride intoxication, it was observed the development of toxic hepatitis in experimental animals, manifested by significant increasing of urea and creatinine levels in the blood serum of animals with a simultaneous decreasing of nitrite anion level. The administration of L-ornithine and L-arginine demonstrates positive impact on liver status and functions by stabilization of cell membranes and regeneration of functional capacity of injured cells. CONCLUSIONS: The results of our study confirm both the presence of unidirectional effects and absence of toxic influences of L-ornithine and L-arginine on liver cells under the conditions of acute carbon tetrachloride intoxication, which are the most important requirements for modern drugs for the treatment of hepato-renal syndrome.

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KEY POINTS: Dietary nitrate supplementation increases plasma nitrite concentration, which provides an oxygen-independent source of nitric oxide and can delay skeletal muscle fatigue. Nitrate supplementation has been shown to increase myofibre calcium release and force production in mouse skeletal muscle during contractions at a supra-physiological oxygen tension, but it is unclear whether nitrite exposure can delay fatigue development and improve myofibre calcium handling at a near-physiological oxygen tension. Single mouse muscle fibres acutely treated with nitrite had a lower force and cytosolic calcium concentration during single non-fatiguing contractions at a near-physiological oxygen tension. Nitrite treatment delayed fatigue development during repeated fatiguing isometric contractions at near-physiological, but not at supra-physiological, oxygen tension in combination with better maintenance of myofilament calcium sensitivity and sarcoplasmic reticulum calcium pumping. These findings improve understanding of the mechanisms by which increased skeletal muscle nitrite exposure might be ergogenic and imply that this is related to improved calcium handling. ABSTRACT: Dietary nitrate (NO3- ) supplementation, which increases plasma nitrite (NO2- ) concentration, has been reported to attenuate skeletal muscle fatigue development. Sarcoplasmic reticulum (SR) calcium (Ca2+ ) release is enhanced in isolated single skeletal muscle fibres following NO3- supplementation or NO2- incubation at a supra-physiological PO2 but it is unclear whether NO2- incubation can alter Ca2+ handling and fatigue development at a near-physiological PO2 . We hypothesised that NO2- treatment would improve Ca2+ handling and delay fatigue at a physiological PO2 in intact single mouse skeletal muscle fibres. Each muscle fibre was perfused with Tyrode solution pre-equilibrated with either 20% ( PO2 ∼150 Torr) or 2% O2 ( PO2  = 15.6 Torr) in the absence and presence of 100 µM NaNO2 . At supra-physiological PO2 (i.e. 20% O2 ), time to fatigue was lowered by 34% with NaNO2 (control: 257 ± 94 vs. NaNO2 : 159 ± 46 s, Cohen's d = 1.63, P < 0.05), but extended by 21% with NaNO2 at 2% O2 (control: 308 ± 217 vs. NaNO2 : 368 ± 242 s, d = 1.14, P < 0.01). During the fatiguing contraction protocol completed with NaNO2 at 2% O2 , peak cytosolic Ca2+ concentration ([Ca2+ ]c ) was not different (P > 0.05) but [Ca2+ ]c accumulation between contractions was lower, concomitant with a greater SR Ca2+ pumping rate (P < 0.05) compared to the control condition. These results demonstrate that increased exposure to NO2- blunts fatigue development at near-physiological, but not at supra-physiological, PO2 through enhancing SR Ca2+ pumping rate in single skeletal muscle fibres. These findings extend our understanding of the mechanisms by which increased NO2- exposure can mitigate skeletal muscle fatigue development.

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OBJECTIVE: Introduction: Nowadays arterial hypertension is supposed to be a pathogenetic factor of numerous cardiovascular diseases (CVD) and 18% cases of the preterm death. Due to the data of the American Heart Association in 77% of patients, who had stroke, the arterial pressure overexceeded 140/90 mm Hg. In Ukraine, according to the epidemiologic study more than 1/3 of the population have increased arterial pressure. One of the extremely important aspects of struggle with CVD is diagnosis and prevention of hypertonic disease. The prevalence of arterial hypertension worldwide increases averagely for 3-4% per year that corresponds with the level of a true epidemy. The aim: Was to evaluate nitrosooxidative status, content of hydrogen sulphide and cortisol in blood serum of patients with a II stage arterial hypertension under the conditions of physical loading. PATIENTS AND METHODS: Materials and methods: 30 patients with II stage arterial hypertension were examined. Examined patients were exposed to two-stage physical loading using veloergometer with the intensity relevant to 50 and 75 % of the proper maximal oxygen uptake (MOU) of the body. RESULTS: Results: In blood serum of patients before and after physical loading the content of TBA-active products, hydrogen sulphide, L-arginine, nitric anion, sum of nitrite-nitrate, cortisol, activity of SOD, catalase and arginase were determined. Significant increase of L-arginine and hydrogen sulphide on the background of the decrease of nitrite-anion and sum of nitrite-nitrate was noted. It may be suggested that in individuals with hypertonic disease under the influence of physical loading synthesis of NO decreases and vasodilatation and vasoprotection occur by means of increase of the hydrogen sulphide level. CONCLUSION: Conclusions: The indices of L-arginine, nitrite-anion and Н2S in blood serum after physical loading reflect the changes in the system of vasodilatation in patients with arterial hypertension. The parameters of gaseous messengers NO and Н2S are the fastest to react to veloergometry on the background of insignificant changes of the level of cortisol, activity of arginase, SOD and catalase in patients with II stage hypertonic disease. Increase of the level of L-arginine and hydrogen sulphide as well as decrease of nitrite-anion level may be considered to be markers of evaluation of immediate changes in patients with arterial hypertension after physical loading.

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OBJECTIVE: to investigate the radiomodifying properties of N-stearoilethanolamine (NSE) in experiment under different conditions of a combined impact of ionizing radiation and stress. METHODS: biochemical, statistical. RESULTS: The radiomodifying properties of N-stearoilethanolamine were revealed under different conditions of a combined impact of ionizing radiation and stress according to the indices of plasma concentrations of TBA-active products, nitrite-anions and catalase activity. CONCLUSIONS: The radioprotective properties of NSE at a dose of 10.0 mg/kg before and after a single total 6.0 Gy irradiation of animals. The radioprotective properties of NSE are identified at a dose of 10.0 mg/kg of animal bodyweight before and after stress. The radiosensitizing properties of NSE occur upon the drug administration in a dose of 10.0 mg/kg before the combined impact of 6.0 Gy ionizing radiation and stress.

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