The effectiveness of the use of oxymethyl uracil on the model of acute alcohol intoxication

Introduction. Considering the prevalence of acute alcohol poisoning in Russia, it seems urgent to search for new effective means of correcting them. Along with taking measures to remove ethanol from the body, pathogenetic correction is effective. Oxymethyluracil and its derivatives have proven to be effective hepatoprotectors in various experimental models of liver damage. The aim of the research was the evaluation of the effectiveness of oxymethyl uracil on the model of acute alcohol intoxication. Material and methods. On the model of acute toxic liver injury of laboratory animals with ethanol, the efficiency of correction of pathological changes with oxymethyl uracil was studied compared to the drug “Mexidol”. A complex of biochemical, morphological and genetic studies was carried out. Results. The morphological studies showed that the correction with oxymethyluracil was more effective at both time points than the drug “Mexidol”, which was manifested in a lower intensity of damage to the liver parenchyma. In the group that received oxymethyluracil, a restoration of the frequency of expression of the Chek 1 gene was observed both after 24 and 72 hours. Upon acute exposure to ethanol, a slight decrease in the level of RIPK1 gene expression was observed. The level of expression of this gene decreased most significantly during the correction of oxy methyl uracil. A decrease in the frequency of expression of this gene can indicate a slowdown in necrosis processes and suppression of reactive oxygen species production in liver cells and, consequently, a curative effect of oxymethyluracil in this type of intoxication. Conclusion. Based on the complex biochemical, morphological and genetic studies carried out, it can be concluded that under acute exposure to ethanol, the corrective effect of oxymethyl uracil is more pronounced than Mexidol (ethylmethylhydroxypyridine succinate).

Histochemical characteristics of nitrergic neuronal system during acute alcohol intoxication and nNOS blockage in the rat lateral septum

Annotation. Alcohol is a one of the most frequently consumed substances of abuse, which can cause addiction or alcohol use disorders (AUDs). Alcohol addiction leads to decrease of the life quality of patients and considerable economic burden. Neuronal mechanisms of addiction are intensively studied. One of the most important systems involved in this process is a brain reward system that includes lateral septum (LS). Additionally alcohol consumption changes activity of the neurotransmitter systems including the nitric oxide (NO). Recent studies for blockage of nitric oxide synthase (NOS) for cocaine addiction and late stages of AUDs demonstrated that a group of the substances known as blockers of NOS can be referred to as candidates for alcohol addiction therapy. The aim of our research was to investigate histochemical characteristics of NO-system in LS, its response to acute alcohol intoxication including or excluding neuronal NOS (nNOS) blockage with selective inhibitor – 7-nitroindazole (7-NI). This study involved three experimental groups of animals (control group (n=4), group with acute alcohol intoxication (n=4), group of nNOS blockage with acute alcohol intoxication (n=4)). For statistical analysis, one-way Kruskal-Wallis test was implemented to reveal differences between groups (Matlab, Mathworks). We have identified NOS-positive structures in LS consisting of big neurons, medium/small neurons and nerve fibers. Acute alcohol intoxication activated subpopulations of NOS-positive medium/small neurons and nerve fibers. Moreover, we determined that ethanol-induced changes can be blocked with selective nNOS inhibitor 7-NI.

DOPAMINERGIC SYSTEM OF THE HYPOTHALAMUS AND STRIATUM OF THE RAT BRAIN WITH THE COMBINED EFFECTS OF ACUTE ALCOHOL INTOXICATION AND PHYSICAL INACTIVITY

Background. The growth of industrialization is accompanied by a decrease in human motor activity, and chronic stress increases the risk of alcoholism. The combination of these factors has a negative effect on the physiological and biochemical processes in the body. Purpose of work. To determine the state of the components of the dopaminergic system in the hypothalamus and striatum of rats during acute alcoholization against the background of hypodynamia. Material and methods. The experiment was carried out on male rats weighing 180-200 g, which, after hypodynamia for a period of 7, 14 and 28 days, were once injected with 25% alcohol at a dose of 3.5 g / kg. The content of the components of the dopaminergic system was determined by high performance liquid chromatography. Results. The striatum is characterized by a decrease in the activity of the dopaminergic system on the 7th day of hypodynamia, followed by its activation with an increase in the period of immobilization to 28 days. In the hypothalamus in the early stages of hypodynamia with subsequent OAI, the changes are poorly expressed, however, on the 28th day, dopamine turnover is activated. Conclusions. The combined effect of acute alcohol intoxication and hypodynamia leads to more pronounced changes in the dopaminergic system in the striatum than in the hypothalamus. Acute alcohol intoxication has a stimulating effect on the dopaminergic system of the hypothalamus and striatum only for long periods of hypodynamia (28 days).