Dmitrii I. Klimenko

The features of the clinical course and the main outcomes at different stages of acute poisoning with barbituric acid preparations are considered.The databases of the Russian National Library, PubMed, Medline, Medscape, eLIBRARY.RU, CyberLeninka were analyzed.During barbiturate poisoning, it is customary to distinguish four consecutive stages depending on the concentration of the substance in the blood, each of which may be accompanied by the development of certain life-threatening conditions. The risk of developing critical conditions is due to a combination of poisoning with another etiology, the presence of concomitant pathology.The complications and outcome of acute barbiturate poisoning largely depend on both the severity of the poisoning and the individual patient profile.Authors’ contribution: Demidova E.O. – research concept, collection and processing of material, writing, editing; Reinyuk V.L. – writing, editing; Kuznetsov S.V. – writing, editing; Klimenko D.I. – writing, editing. All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.Conflict of interests. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.Funding. The study had no sponsorship.Accepted: January 14, 2025 / Revised: March 26, 2025 / Received: November 25, 2025 / Published: January 15, 2026

BACKGROUND: The stability of trace element composition within the organism is crucial for maintaining the vital biochemical and biophysical processes. The severity of diseases associated with heavy metal accumulation is largely attributable to the irreversibility of this process and the persistent disturbances in metabolic systems. Therefore, investigating the imbalance of biogenic elements in patients with chronic heavy metal intoxication is highly relevant. AIM: The work aimed to determine the variations in the levels of biogenic metals and selenium in patients with chronic manganese chloride intoxication. METHODS: The experiments were conducted on 12 male white outbred rats weighing 180–220 g. The experimental group (n=6) received a 0.2% manganese chloride solution via automatic dispensers for 3 months, and the control group (n=6) was given tap water. The concentrations of manganese, copper, zinc, selenium, calcium, iron, and magnesium were measured in the left and right hippocampi using atomic emission spectroscopy with PerkinElmer Optima 7000 DV ICP-OES Spectrometer (USA). RESULTS: Based on the hippocampal content, the analyzed biogenic elements were arranged in the ascending order of concentration as follows: [Mn] [Cu] [Zn]=[Se] [Mg] [Fe] [Ca]. No evidence of asymmetry was observed in the levels of these metals and selenium across any of the animal groups. In rats that received the manganese solution, the hippocampal levels of manganese were more than twice as high compared to the control group (p 0.01). In the experimental group, the copper concentrations were found to be significantly higher (p 0.01), whereas the selenium levels were lower (p 0.01) compared to the control group. These effects demonstrated a bilateral pattern, affecting both the left and right hippocampi. The levels of iron, zinc, calcium, and magnesium remained unchanged. CONCLUSION: It can be hypothesized that the observed variations in biogenic elements may be responsible for the impairment of enzymatic systems, which include manganese, copper, and selenium.

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

BACKGROUND: The incidence of bipolar disorder is increasing worldwide. The search for new compounds with antidepressant activity and milder adverse drug reactions is an urgent task of modern psychopharmacology. AIM: This study aimed to analyze the effect of new neuroactive coumarin derivatives on the level of depressive behavior and monoamine metabolism in the brain structures of rats. MATERIALS AND METHODS: The antidepressant effects of LVM-091, LVM-099, LVM-S144, and IEM-2886 were evaluated in rats subjected to the Porsolt forced swimming test and the metabolism of monoamines in brain structures (LVM-099) using high-performance liquid chromatography. RESULTS: LVM-091, LVM-099, LVM-S144, and IEM-2886, synthesized from coumarin, decreased the immobilization time of the experimental rats in the Porsolt forced swimming test, indicating the antidepressant effect of these substances. The administration of LVM-099 at a dose of 10 mg/kg increased the level of homovanillic acid and the homovanillic acid-to-dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid levels and the 5-hydroxyindoleacetic acid-to-serotonin ratio in the nucleus accumbens. In the amygdala, the levels of norepinephrine, dopamine, serotonin, and their metabolites did not change after LVM-099 administration. CONCLUSIONS: New coumarin derivatives exert antidepressant effects and increase the metabolism of dopamine and serotonin in rat nucleus accumbens, which can be used in the development of new highly effective antidepressants.

BACKGROUND:The compound 2-aminobenzothiazole (2-ABT), which has a proven antihypoxic effect, was studied at the Department of Pharmacology of the Kirov Military Medical Academy. The mechanism of action of this substance is partially associated with the central action, and its protective effect may be due to the general hypothermic effect. AIM:To determine the effect of 2-ABT on body temperature. MATERIALS AND METHODS:Twenty-four male adult white outbred mice were studied. Moreover, 2-ABT was dissolved in 0.9% sodium chloride solution and administered intraperitoneally to mice at doses of 32.5 mg/kg (with proven antihypoxic effect), 21.7 mg/kg, and 10.8 mg/kg. Rectal temperature was obtained with an electronic thermometer (DT-623, China) before administration of the test substance and at 5, 30, and 60 min after the injection. RESULTS:Compound 2-ABT has a pronounced dose-dependent hypothermic effect. This effect is maximally expressed in a dose in which the compound has a proven antihypoxic property — 32.5 mg/kg. The hypothermic effect was evident within 5 min after administration. Additionally, the maximum decrease in body temperature was observed after 30 min, whereas the effect persisted for 1 h. CONCLUSIONS:2-ABT may be a promising compound for developing a drug for drug-induced (controlled) hypothermia.

Changes in biochemical parameters of blood serum and monoamine metabolism in the brain were studied on male white outbred mice subjected to intraperitoneal injections of 1-methyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (MPTP-F). The levels of norepinephrine, dopamine, serotonin and their metabolites — dioxyphenylacetic, homovanilinic and 5-hydroxyindolacetic acids — were neasured by HPLC in the cerebral cortex, hippocampus, olfactory tubercle and striatum of the right and left sides of the brain. The treatement with MPTP-F did not lead to significant changes in the biochemical parameters of blood serum. An increase in the norepinephrine concentration a decrease in the dopamine level in the right striatum were found in animals treated with MPTP-F. No changes were detected in other studied brain areas. It has been suggested that the effect of the neurotoxin MPTP-F is determined by several factors, i. e. the lipophilic properties of the molecule, the quantitative distribution of dopamine neurons between right and left sides of the brain, differences in the linear velocity of blood flow through the right and left carotid arteries and the state of the blood-brain barrier. The results obtained may indicate the prospects of using MPTP-F for modeling the early stage of Parkinson’s disease.