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Introduction. In Russia, the problem of toxic hepatitis is of great importance and relevance. The etiology of toxic hepatitis (industrial toxicants, drugs, ethanol) and, as a consequence, pathogenesis may have significant differences at the molecular genetic level. The aim of the study was to analyze the expression of genes involved in the response to toxic liver damage of various etiologies. Material and methods. Toxic hepatitis was modulated in male albino mongrel rats weighing 180-200 grams assigned to four groups (control group, carbon tetrachloride, paracetamol, ethanol). After 24 and 72 hours of paracetamol administration, rats were anesthetized and the mRNA levels of the Chek1, Gclc, Gstm1, Gstp1, Gstt1, Nfe2l2, Nqo1, Ripk1 genes in the liver homogenate were examined. Results. As a result of the analysis of the genes expression studied, the expression profile was found TO be differed depending on the etiology of toxic hepatitis. With carbon tetrachloride poisoning, an increase in the expression of the Nqo1 genes (p = 0.001), Gstm1 (p = 0.037) and a decrease in the expression of the Nfe2l2 genes (p = 0.004), Ripk1 (p = 0.004) was observed. With the liver damage by paracetamol and its metabolites, opposite to the expression of the Gstm1 gene (p = 0.001) decreased, and the expression of the Nfe2l2 (p = 0.009), Gclc (p = 0.001), Chek1 (p = 0.011) genes increased. During alcohol intoxication, there were no statistically significant changes in the expression profiles of the genes studied. Conclusion. the results obtained may indicate the involvement of various molecular genetic mechanisms in the process of response to toxic liver damage, depending on the etiology.

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Introduction. Acute liver damage with ethanol and its surrogates and chemicals remains an urgent problem. Therefore, studies of the use of hepatoprotector in acute liver damage by various toxicants in the experiment are relevant. The purpose of this study is an experimental evaluation of the use of ademetionine in the early stages of the toxic effects of carbon tetrachloride and ethanol. Materials and methods. The therapeutic effect of the drug “Heptor” in acute intoxication with carbon tetrachloride (subcutaneous administration at a dose of 2 g/kg) and ethanol (oral administration at a dose of 4 g/kg weight) was studied. Studies of metabolic processes in the liver were carried out based on biochemical parameters of rat blood serum. Results. The studies showed that normalization of metabolic processes was observed after introducing “Heptor” against the background of exposure to both toxicants. The therapeutic effect of ademetionine in the case of carbon tetrachloride intoxication had a positive impact after 24 hours of administration and persisted after 72 hours of the experiment. These provisions were based on the results obtained: the restoration of the activity of marker enzymes of hepatocytes (AsAT, AlAT, LDH), the concentration of uric acid and cholesterol, and the indicators of protein metabolism were revealed. The introduction of ademetionine after ethanol intoxication helped restore the function of hepatocytes, which led to the normalization of protein metabolism. The drug stopped hyperenzymemia, which confirmed its membrane-protective properties. Conclusion. “Heptor” has a regenerating, detoxifying and membrane-protective effect in acute liver lesions with carbon tetrachloride and ethanol. The obtained data confirm the universality of this drug, based on the possibility of using various mechanisms of therapeutic action, which allows us to recommend ademetionine as a hepatoprotector to prevent early liver damage when exposed to high doses of multiple toxicants.

Introduction. The high frequency of chemical poisoning is accompanied by an increase in the absolute number of cases of chemical damage to the liver. There is growing evidence that acute chemical poisoning in Russia is among the leading non-infectious diseases leading to premature death of male and female working-age people. It seems relevant to search for new pharmacological agents with low toxicity and high hepatoprotective activity, which increase the body’s stability under the influence of adverse environmental factors. The use of metabolic action drugs combining antioxidant and antihypoxic activity as hepatoprotectors is promising. The purpose of this study is an experimental evaluation of the hepatoprotective activity of a new composition of oxymethyluracil with succinic and fumaric acids. Material and methods. The composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids was first synthesized at the Ufa Institute of Chemistry. Using the model of acute liver toxic damage with carbon tetrachloride in laboratory animals, the prophylactic effect of a new drug was studied in comparison with heptor (ademetionine). Biochemical and morphological studies of laboratory animals’ biomaterial were conducted. Results. The analysis showed that when using the studied drugs, biochemical parameters were close to the level of control animals. Morphological changes in the liver were less pronounced in the group of animals treated with the new composition, compared with changes in the structure of the liver of animals treated with heptorator (ademetionin). Conclusion. The new composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids has a protective effect on the liver of laboratory animals with the acute toxic effects of carbon tetrachloride, comparable, and in some cases, exceeding the preventive effect of heptoperam (ademetionine).