Introduction: High-volume manufacturing of selenium and a widespread use of its compounds pose potential risks to human health. Certain copper production processes emit selenium-containing nanoparticles. Objective: To assess health effects of selenium oxide nanoparticles as an industrial and environmental toxicant. Materials and methods: Selenium oxide nanoparticles (SeO NPs) were obtained by laser ablation. Their toxicity was studied both in vitro on human lung-derived embryonic fibroblasts (FLEH-104 cell line) by assaying adenosine triphosphate (ATP) bioluminescence and the rate of oxygen consumption, and in vivo on outbred albino rats by analyzing ultrastructural changes in tissues using electron microscopy, measuring succinate dehydrogenase activity of blood lymphocytes, and conducting a blood-based metabolomic test. Results: The in vitro experiment showed a decrease in ATP bioluminescence by 75.9 % and in the oxygen consumption rate of cells by 79.8 % in the incubation medium with 100 μg/mL concentration of SeO NPs. In the in vivo experiment, succinate dehydrogenase activity of blood lymphocytes decreased inversely with the increasing dose by 10.12 %, 14.0 %, 15.9 % compared to the control animals in the SeO NPs 0.1, SeO NPs 0.5, and SeO NPs 1 exposure groups, respectively. The study of ultrastructural changes in liver tissue showed a smaller number of normal mitochondria (7.78 % less in the SeO NP 1 group) compared to the controls while the metabolomic test revealed decreased acylcarnitines and increased lysophosphatidylinositols following the exposure to SeO NPs (p > 0.05). Conclusion: The results of our in vitro and in vivo studies showed adverse effects of SeO NPs on bioenergetics processes in cells involving at least two mechanisms: disruption of mitochondrial β-oxidation of fatty acid and inactivation of succinate dehydrogenase. The fundamental role of the latter in the mitochondrial electron transport chain makes its vitally important for most multicellular organisms. Our findings can serve as a rationale for assessing selenium-containing nanoparticles as a chemical hazard and searching for approaches to managing their health risks.

Introduction: In the developed metallurgical industry, maximum permissible concentrations of heavy metals in the work environment are often exceeded, and the elevated exposure levels have a detrimental effect on workers’ health. Heavy metals cause oxidative stress, which is key factor in the development of atherosclerotic lesions. Atherosclerosis, in its turn, is the primary cause of heart attacks and stroke, which account for 85 % of all deaths from cardiovascular diseases. Objective: To study molecular mechanisms of atherosclerosis and the impact of heavy metals on the disease course. Methods: We applied methods of information analysis based on the review and generalization of published up-to-date research data on the pathogenesis and effects of heavy metals on the course of atherosclerosis found in NLM, Scopus, CyberLeninka, Google Scholar, and eLibrary abstract and citation databases, as well as on information portals, as of January 2022. More than 400 papers were analyzed and 66 full-text articles were found eligible for inclusion in this review. Results: We established the relationship between the exposure to heavy metals and the molecular mechanisms of atherosclerosis and compared the main stages of the disease development with the respective blood metabolomic profiles. Conclusions: Our literature review has revealed problems in the regulatory framework and practical assessment of the contribution of heavy metal exposures to the course of atherosclerotic lesions. So far, the effect of heavy metals only on isolated processes of the pathogenesis of atherosclerosis has been established, such as a change in permeability and destruction of vascular membranes, increased oxidative stress, inflammation, proliferation of smooth muscle cells, changes in blood rheological properties, and an increased risk of thrombosis. The observed patterns in the change in concentrations of some blood metabolites and the potential adverse vascular effect of heavy metals will help develop new methods for detecting atherosclerosis and include industrial workers in the group at risk of the disease for its early diagnosis.

Introduction. The prevalence of lead in the environment, due to human production and economic activities, and the xenobiotic nature of the element substantiate the relevance of studying the changes caused by the action of this metal. Materials and methods. A non-target metabolomic screening of the blood of rats exposed to intraperitoneal administration of lead acetate by HPLC-mass spectrometry was carried out. The expression of the selected masses was compared with those for the control group of animals. The masses that significantly changed the intensity compared to the control were subjected to fragmentation to obtain characteristic fragments. The annotation of metabolites was performed by searching in MS/MS databases and by comparison with in silico fragmentation spectra. The involvement of annotated metabolites in metabolic processes was established by literature analyzing. Results. Non-target metabolomic screening revealed 37 m/z values for the exposed group, significantly changing the intensity compared to the control. Annotation using fragmentation spectra and in silico fragmentation allows establishing the structure of eight metabolites, including an epoxy derivative of linolic acid, 15-hydroxyeicosatetraenoic acid, four oxo- and hydroxyacylcarnitine derivatives of long-chain fatty acids, one acylcarnitine derivatives of medium-chain fatty acids and one lysophosphoserine. Conclusion. Analyzing the literature, the known functions of the identified metabolites were established and attributed to the known metabolic processes. So, oxo- and hydroxyacylcarnitines are derivatives for intermediate products of β-oxidation fatty acids - it is increased concentration compared to the control indicates a violation of this process under the influence of oxidative stress caused by lead. Epoxy and 15-hydroxy derivatives of fatty acids (increased content relative to the control group) act as regulatory metabolites (vasodynamic activity), on the one hand, and markers of lead-induced hypoxia on the other hand. The increase of the concentration for the lysophosphatidylserine derivative indicates the intensification of apoptotic processes in the organism of the exposed group in contrast to the control.

Copper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning.

INTRODUCTION Environmental pollution with heavy metals is vital issue in the present time. Lead, as one of the environmental contaminators, deserves attention due to its applicability in human activity and its xenobiotic character. METHODS In this study we used an untargeted metabolomic approach -the metabolomic fingerprinting method. Lead acetate was intraperitoneally injected to rats within the framework of a subchronical experiment and blood samples were analyzed by UHPLC-MS. Metabolite expression was qualitatively compared between treated and control groups. For substances with a significant content difference, tandem CID spectra for structure elucidation were obtained using an exact mass search by generating a list of potential formulas, by a characteristic fragments database search, using in silico mass spectra prediction, and by looking for a specific fragmentation rearrangement. RESULTS Untargeted metabolomic analysis shows 37 metabolites with significant changes in expression in comparing the control and exposure group. Annotation