Introduction. Oxymethyluracil is an effective antihypoxant in a model of histotoxic hypoxia. Acetylcysteine combines the properties of a toxicotropic nonspecific and toxicokinetic antidote, promotes the synthesis of glutathione in the body. The aim of the research was a preliminary assessment of the antihypoxic properties of the complex compound of oxymethyluracil with acetylcysteine in the model of histotoxic hypoxia. Materials and methods. To study the antihypoxic properties, a model of acute histotoxic hypoxia was used. The studied compound was injected into the abdominal cavity of experimental mice three times with an interval of 30 minutes at 100 and 500 mg/kg of body weight, then after 30 minutes the toxicant was introduced. Comparators were oxymethyluracil and acetylcysteine. Results. The complex compound of oxymethyluracil with acetylcysteine in the model of acute histotoxic hypoxia statistically significantly was established to increase the lifespan of mice at a dose of 500 mg/kg of body weight. A dose of 100 mg/kg of the compound is practically ineffective. Limitations. The limitations of the study are related with antihypoxic properties of the new complex compound of oxymethyluracil with acetylcysteine previously studied in one model of hypoxia (histotoxic), because oxymethyluracil (as an antihypoxant) is most effective in this experimental model. For a final judgment on the antihypoxic properties of the studied compound, it is necessary to continue studies on other models of hypoxia. In addition, in order to identify possible synergism (potentiation) of the action of oxymethyluracil and acetylcysteine, it seems appropriate to conduct studies to evaluate the antihypoxic effect with their simultaneous administration (in the form of a simple mixture). Conclusion. A new complex compound of oxymethyluracil with acetylcysteine can be recommended for further wider (preclinical) research as a potential antihypoxant.

Introduction. In modern conditions, caused by the pandemic of a new type of viral infection Covid 19, the use of paracetamol, which has hepatotoxic properties in overdose, has increased. It seems relevant to study metabolic disorders in the liver in acute paracetamol intoxication and evaluate the effectiveness of the timely use of hepatoprotective drugs. The purpose of this study is an experimental assessment of metabolic changes at the early stages of paracetamol exposure and pharmacological correction of toxic liver lesions with oxymethyluracil in comparison with known hepatoprotectors - ademetionine and Mexidol. Material and methods. Acute intragastric administration of paracetamol to laboratory animals was performed, and the corrective effect of the drug oxymethyluracil was studied in comparison with “Heptor” and “Mexidol”. Biochemical studies of biomaterial of laboratory animals were conducted. Results. The analysis found the use of known hepatoprotectors and oxymethyluracil after exposure to paracetamol to normalize the biochemical parameters that characterize the functional state of the liver in laboratory animals. Conclusion. Oxymethyluracil, along with known hepatoprotectors, has a protective effect on the liver of laboratory animals under acute exposure to paracetamol comparable to, and in some cases exceeding, the corrective action of “Heptor” and “Mexidol”.

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).

The paper presents the results of studies of metabolic changes in the blood serum of rats on the background of oral administration of cadmium chloride for 2 months. Elevated serum hepatic enzymes are the main indicator of damage to hepatocytes caused by cadmium poisoning. It was shown that in three experimental groups of rats, which were intragastrically injected with CdCl2, the level of activity of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase was significantly increased compared to the control; on average, the increase in biochemical parameters was 31.8%, 12.9% and 21.9%, respectively. A decrease in the alkaline phosphatase activity in the blood serum of experimental animals, depending on the increase in the dose of the pollutant, is a consequence of the degree of heavy metal damage to the epithelium of the bile ducts. High levels of biochemical parameters of the renal profile, uric acid (UA) and urea, due to impaired glomerular filtration are shown. The noted decrease in the concentration of UA (by 22,3 %) in the 1st experimental group of rats to the level of 87,4±11,6 μmol/L, relative to the negative control (112,5±4,0 μmol/L), indicates a general pathology of the urinary systems induced by heavy metal. The revealed deviations in the indicators of the main biochemical markers of liver and kidney damage serve as a reliable argument characterizing cadmium as a pronounced hepato- and nephrotoxicant.

Introduction. This article presents the results of experimental simulation of the acute toxic effect of cadmium on the rat organism, its distribution in the liver, and kidneys. Activation of the protective mechanism against toxic metal through the metallothionein protein has to reduce the bioavailability of free cadmium. Material and methods. The study was conducted on rats weighing 140-190 g, which was once intragastrically injected with cadmium chloride in an amount of 1/20 LD50. We studied the time intervals: before intoxication, 1, 2, 4, 6, 24, 48, and 96 hours after inoculation. The accumulation of cadmium in the liver and kidneys was measured by atomic absorption spectrometry. The expression of the metallothionein gene (МТ1, МТ2А, МТ3) was determined using RT-PCR on RNA isolated from the same organs. Results. Quantitative differences in the metal content in the liver and kidneys are observed 1 hour after intoxication, with a cadmium content of 250 and 125 times higher than in the control groups, respectively. There is an accumulation of cadmium in the liver with a maximum after 6 hours, and then its redistribution to the kidneys. The pronounced expression of metallothionein with a single acute exposure to cadmium is tissue-specific, so the expression of the MT1 and MT2A genes was greatest in the liver and the MT3 gene in the kidneys. Discussion. After administration cadmium is mainly localized in hepatocytes and its concentration may exceed the ability of metallothionein to bind cadmium ions, which leads to histopathological changes in the liver. In response to the intake of metal in the cell, the expression pattern of many genes, including those associated with the activation of protective reactions, changes. Conclusion. Our data show a single exposure to cadmium to lead to an increase in the content of MT transcript in the liver and kidneys, simultaneously with the accumulation of metal in them. The nature of this accumulation depends on the organ, on the time of exposure, and gene expression also on the form of MT.