No 3 (2019)

Four polymorphic GABRA2 gene variations: rs105733011, rs8168342, rs198286814, rs198837638 that can influence the formation of different biological effects of the organism when exposed to ethanol have been investigated. For rs105733011 polymorphism the frequency of occurrence of the CT genotype was found to be significantly higher (p < 0,05) among animals with «severe intoxication» – 37,0% than with «mild intoxication» – 14,0%. For rs198286814 polymorphism the tendency to the most frequent occurrence of the AG genotype in the group of animals with «severe intoxication» was established. Significant differences in the distribution of occurrence frequencies of the GG/AG genotypes in the studied groups for polymorphic loci rs8168342 and rs198837638 were not revealed. It was concluded that the rs105733011 polymorphism can be one of the genetic markers allowing to predict the degree of inhibitory action of ethanol in acute alcohol intoxication.

When modeling myeloablation cytostatic chemotherapy with cyclophosphamide in rats fulminant hyperammonemia was observed accompanied by an increase in the content of ammonia and glutamine, a decrease in the content of pyruvic and lactic acids in brain tissue. A positive correlation between the indicators of azotemia and the content of ammonia and glutamine in brain tissue was established. In loading test with ammonium acetate changes in the chemical composition of blood and brain tissue were more pronounced. The data obtained indicate the intensification of the intake of gastrointestinal ammonia into the brain from the blood, which leads to the depletion of the tissue pool of pyruvate with the introduction of cyclophosphane in doses used for myeloablation. Such changes create the conditions for disruption of energy supply of neurological functions during myeloablative cytotoxic chemotherapy using cyclophosphamide.

One of the urgent tasks of clinical toxicology is the development of therapy aimed at stoichiometric and/or catalytic detoxification of organophosphorus compounds in the bloodstream, which will prevent the poison’s entering the neuromuscular and neuronal synapses and help to avoid irreversible consequences of poisoning. An auxiliary option for the detoxification of organophosphorus compounds in the bloodstream may be a directed effect on albumin, the main transport protein of the blood, by means of molecules modulating its binding and/or esterase properties. The aim of the present study is to evaluate the effect of fatty acids on the binding and esterase activity of human albumin to organophosphorus compounds by molecular modeling methods on the example of paroxone and oleic acid. According to the data obtained, an increased concentration of fatty acids in the blood reduces the likelihood of paraoxon binding to albumin and pseudo-esterase reaction.

The article on the basis of an analysis of the literature discusses promising areas for the development of antidote prophylaxis and treatment of acute cyanide poisoning. The chemical compounds mediating anticyanide activity by stimulating the main detoxification mechanisms of endogenous cyanide: sulfangen, cobinamide, α-ketoglutaric acid claimed to be potential cyanide antidotes, effective and safe for intramuscular and intraosseous injections, inhalation and oral administration.

The resorptive effects of 0.01 M cerium nanodioxide sol upon single intraperitoneal administration to rats have been studied. The acute exposure to nanoparticles was found to have a dose-dependent general toxic effect on the body (weight loss, inflammatory changes in the abdominal organs, modification of individual behavior, hematological changes, metabolic imbalance), which develops on the background of POL activation. The prooxidant effect of cerium dioxide nanoparticles is demonstratively manifested at relatively high exposure levels (80–8 mg / kg). The threshold dose for the general toxic effect (Limch integr) is equal to 0.8 mg / kg.