STUDY OF THE HEPATOPROTECTIVE EFFECT OF EXTRACTS FROM NATIVE AND DISPERSED BIRCH BARK IN CASE OF CARBON TETRACHLODIDE INTOXICATION

The hepatoprotective effect of aqueous alcoholic extracts obtained from the raw materials of native birch bark (NBBE) and previously dispersed to a particle size of 100–300 nm (DBBE) was studied in male rats. The animals were divided into 14 groups of 10 animals each. Groups 1, 2 — intact; 3, 4 — control (carbon tetrachloride); 5, 6 — previously, for 5 days, NBBE was injected once intragastrically at a dose of 50 mg/kg, on the 6th day, a 50 % oil solution of CC14 was injected at a dose of 0,2 ml/100 g abdominally; 7, 8 — DBBE at a dose of 50 mg/kg + CC14; 9, 10 — NBBE at a dose of 100 mg/kg + CC14; 11, 12 — DBBE at a dose of 100 mg/kg + CC14; 13, 14 — the comparison drug carsil was injected at a dose of 100 mg/kg + CC14. On the 4th and 7th day after the injection of CC14, the animals were removed from the experiment. The data obtained indicate the hepatoprotective effect of NBBE and DBBE in carbon tetrachloride intoxication, which was expressed in the necrosis volume density decrease due to their preliminary preventive injection. NBBE at a dose of 100 mg/kg has a more significant protective effect compared to Carsil. Prophylactic injection of DBBE at doses of 50 and 100 mg/kg not only prevented the development of necrosis in the liver, but unlike Carsil, it activated intracellular processes of reparative regeneration in the recovery period, which is confirmed by an increase in the number density of binuclear hepatocytes.

THE EFFECTS OF L-ORNITINE AND L-ARGININE ON THE PROCESSES OF LIPID PEROXIDATION IN THE FUNCTIONAL LAYERS OF KIDNEYS ON THE BACKGROUND OF ACUTE TOXIC HEPATITIS

The aim is to evaluate the effects of L-arginine and L-ornithine on the processes of lipid peroxidation in homogenates of renal cortex, renal medulla and renal papilla under conditions of acute toxic hepatitis. 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 mlxkg-1 of body weight and simulation of treatment by administration of normal saline in equivalent doses), acute carbon tetrachloride hepatitis + L-ornithine (1000 mgxkg-1), acute carbon tetrachloride hepatitis + L-arginine (500 mgxkg-1) and acute carbon tetrachloride hepatitis + combination of substances. Results: On the background of acute carbon tetrachloride intoxication it was observed the development of renal failure in experimental animals, manifested by activation of lipid peroxidation processes in homogenates of renal cortex, renal medulla and renal papilla. The administration of L-ornithine and L-arginine demonstrates positive impact on renal function and hepato-renal syndrome by stabilization of cell membranes and regeneration of functional capacity of injured renal 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 renal 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.

The role of differences of metabolism in the formation of disorder of function of the liver and the kidney in tetrachloride carbon intoxication

Currently, there is a steady tendency for the growth of diseases of the hepatobiliary system, which is caused by a complex of endogenous and exogenous influences. Therefore, treatment of chronic hepatitis remains one of the important and complex problems in the general medicine clinic. The purpose of the study is to evaluate the role of some regulatory mechanisms in the formation of liver and kidney disorders in carbon tetrachloride intoxication. The experimental studies were performed on 54 white Wistar rats of the autohybrid breeding line, which were divided into control and experimental groups. Within 7 days, the experimental group of animals was subjected to carbon tetrachloride intoxication by administering 0.5 ml CCl₄ subcutaneously. Kidney function status was assessed by changes in diuretic diuresis, glomerular filtration function, percent tubular reabsorption, serum creatinine and urea content, chloride excretion and urine pH. Liver function was assessed by ALT and AST activity, bilirubin in the blood, serum creatinine and urea content, total serum protein. The status of other aspects of metabolism was evaluated by MDA composition and catalase activity; NO content, uric acid, Na⁺/K⁺ and Ca⁺²/Mg⁺² activity — ATP-az. Changes in the overall blood count as well as the state of the regulatory components of the immune response by the content of circulating immune complexes and the content of heterogeneous antibodies were evaluated. The data obtained were subjected to standard statistical processing using a coefficient of authenticity. As a result, changes in kidney and liver function, characteristic of the development of hepatorenal syndrome, have been established. According to the results of the study, it is concluded that the systemic metabolism of the animal body changes due to the violation of the properties of cell membranes, slowing the flow of intracellular processes of life, which disrupts the elimination of xenobiotics and plays a negative role in the pathogenesis of hepatorenal insufficiency.

Mitochondrial dysfunction and compensatory mechanisms in liver cells during acute carbon tetrachloride-induced rat intoxication

Electron-transport chain and redox-balance of mitochondria are important targets that are damaged during intoxication. The aim of the present work was to estimate the role of impairments in cellular bioenergetic function in the development of liver damage during acute carbon tetrachloride intoxication in rats and to elucidate possible compensatory mechanisms. Acute CCl 4 –induced rat intoxication (0.8 g/kg or 4 g/kg) resulted in considerable impairments of respiratory and synthetic mitochondrial functions; their manifestations depended on the dose of the toxic agent and the duration of the intoxication increased and accompanied by complete uncoupling of oxidation and phosphorylation processes in liver mitochondria. The intoxication induced considerable liver damage and accumulation of NO in blood plasma and liver tissue. The changes of some parameters of liver mitochondrial functional activity demonstrate an oscillative pattern, reflecting compensatory mechanisms during intoxication that involved increased reduced glutathione level and enhanced succinate dehydrogenase activity.