Mikhail Evgen’eVich Shemaev

Neurotoxicity is a manifestation of intoxication with lead compounds. When developing new drugs for the treatment of lead poisoning, modern methods for assessing the neurotoxic effect of such compounds are of great importance. In view of this, we aimed to study long-term manifestations of lead neurotoxicity using a computerized test system for quantitative assessment of the startle reflex in laboratory animals – the TSE Startle Response System (“TSE”, Germany). Outbred male rats weighing 180–220 g were selected as a test system. The animals were randomized into control and experimental groups. The experimental group received a single intraperitoneal injection of lead acetate at a dose of 300 mg/kg. In the surviving animals, sensory responses were assessed on days 3 and 29 using the neurophysiological test of response to a sudden stimulus, the Startle Response System. In both the shortand long-term periods of acute lead intoxication, a decrease in responses to light, noise, and electrical pain stimuli was noted, which may be a consequence of lead accumulation in brain tissue.

BACKGROUND: The pathogenesis of the long-term effects of neurotoxic agents remains poorly understood. Tissue specificity, as a qualitative characteristic of the toxic effect, involves selective metabolic process remodeling in specific tissues. AIM: The work aimed to evaluate the tissue specificity of metabolic changes in the long-term effects of acute toxic exposure. METHODS: An experimental study was performed on rats. The toxic agents used were 1.6 mg/kg of phenylcarbamate, 11.5 g/kg of methanol, and 300 mg/kg of lead acetate. The parameters of lipid peroxidation and the antioxidant system were determined using standard biochemical techniques on day 30 after toxic exposure. RESULTS: In the groups of intact animals and those that survived the exposure, lipid peroxidation and the antioxidant system were found to be tissue-specific. The most significant effect, which was common for body tissues, was the shift in diene conjugates, as toxic exposure was followed by a significant decrease in tissue specificity. Regarding the tissue concentration of malondialdehyde, which shows the activity of lipid peroxidation, phenylcarbamate and lead induced an increase in tissue-specific response to toxic effects. This finding showed the selective effect on individual links of oxidative stress in tissues. CONCLUSION: Lipid peroxidation and antioxidant system activity can be considered markers for evaluating the effect of toxic agents on metabolic processes in various tissues. A higher brain tissue sensitivity to the toxic effects can be demonstrated by a higher growth rate of diene conjugates (phenylcarbamate and lead acetate), glucose-6-phosphate dehydrogenase, and superoxide dismutase (methanol). A hepatic tissue-specific response was evidenced by increased activity of glucose-6-phosphate dehydrogenase (phenylcarbamate and methanol) and decreased activity of superoxide dismutase (methanol and lead acetate). The kidneys were particularly susceptible to the impaired utilization of reduced glutathione (methanol) or its formation (lead acetate). The compensatory activation of superoxide dismutase (methanol and lead acetate) was a marker of splenic tissue-specific response.

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.

Introduction. Heavy metals have a serious toxic effect on the human body. The availability of adequate models for the elimination of toxicants and the testing of enterosorbents based on them will improve the quality of poisoning therapy. Material and methods. To assess the effectiveness of the sorbent, a formalized model based on data on the cumulative excretion of cadmium in urine and feces for 20 days was used. Intramuscular priming with cadmium acetate was carried out during the first three days of the experiment at a daily dose of 3 mg/ kg, the enterosorbent was administered orally at a dose of 100 mg/kg during the study. The cadmium content in the biological media was determined by methods of inversion voltammetry. Results. During the experiment, no more than 3% of the injected toxicant was removed from the animals of both groups. The enterosorbent in the conditions of the experiment did not change the amount of cadmium excreted, but affected the redistribution between the renal and intestinal elimination streams. A significant effect of the enterosorbent on the cadmium content in the liver was noted. Limitations. Evaluation of the effect of the drug on the elimination of the toxicant was carried out for a limited period of time. Additional experiments with longer observation periods and other metals and their dosages would allow to reveal in more detail the beneficial properties of the studied drug. Conclusion. A significant effect of the enterosorbent on the cadmium content in the liver was noted. There may be a secondary intake of cadmium into the blood from the intestine and a negative effect of this process on kidneys.