Scientific and methodological grounds for iterative prediction of risk and harm to human health under chemical environmental exposures: From protein targets to systemic metabolic disorders

UDC: 
57.044; 616.092
DOI: 
10.21668/health.risk/2024.2.02.eng
Authors: 

N.V. Zaitseva1,2, M.A. Zemlyanova1, Yu.V. Koldibekova1, E.V. Peskova1

Organization: 

1Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya St., Perm, 614045, Russian Federation
2Russian Academy of Sciences, Department of Medical Sciences, 14 Solyanka St., Moscow, 109240, Russian Federation

Abstract: 

Increasing the predictive potential of early diagnostics and correction of negative outcomes is becoming especially relevant for preventing and reducing personalized and population health risks, including those caused by environmental exposures. The purpose of the study was to develop scientific and methodological grounds for iterative numerical prediction of risk and harm to human health under chemical environmental exposures. The study design was based on the consistent implementation of an algorithm for system analysis of the development of negative effects under a chemical environmental exposure, from protein targets to systemic metabolic disorders. The in-depth examination covered more than 1 million people living under real long-term combined inhalation exposure at doses up to 5–10 RfC. About 350 digital multifactor models, including about 5.5 thousand parameters, were evaluated.

Structural bioinformation matrices were constructed to identify the sequence of response events at the molecular-cellular level. These events are initiated by the transformation of the protein-peptide profile of human blood plasma, which determine the metabolome. The study clarifies the elements of involvement of 20 target proteins in the pathogenesis of metabolic disorders associated with hypertension, dyslipidemia, obesity, hepatosis, and cognitive dysfunction associated with chemical combined exposure. The criteria for the safe content of 10 contaminants were substantiated, taking into account their combinations in human biological media. Predictive assessments of pathogenetic pathways were confirmed by the facts of their implementation at the cellular-tissue, organ and body level as metabolic disorders and existing diseases of the cardiovascular, nervous systems, lipoprotein metabolism, etc., proven to be associated with effects produced by airborne pollutants, including combined ones.

The study expands the existing methodological approaches to assessing combined effects of chemicals taking into account parameterized cause-effect relations of biomarkers of exposure and effects and quantitative assessment of additional cases of risk occurrence. Assessment of the developed digital models revealed that combined chemical exposures were predominantly synergic and emergent (up to 70 % cases). We developed conceptual grounds and architecture of iterative risk prediction and the development of risk-associated diseases, including real harm to health upon elevated expression of protein targets. Thus, the digitized version of the forecast (digital platform), as a multi-level cascade model, is a tool for scientific analysis of a hygienic situation with the parameterization of expected negative outcomes. It determines methods for their correction and prevention, which increases the reliability of hygienic assessments and the validity of management decisions.

Keywords: 
health risk, caused harm, environmental factors, target proteins, negative effect, cascade model, cause-effect relations, forecast, digital platform
Zaitseva N.V., Zemlyanova M.A., Koldibekova Yu.V., Peskova E.V. Scientific and methodological grounds for iterative prediction of risk and harm to human health under chemical environmental exposures: from protein targets to systemic metabolic disorders. Health Risk Analysis, 2024, no. 2, pp. 18–31. DOI: 10.21668/health.risk/2024.2.02.eng
References: 
  1. Onishchenko G.G. Development of the risk analysis methodology given the current safety challenges for public health in the Russian Federation: vital issues and prospects. Health Risk Analysis, 2023, no. 4, pp. 4–18. DOI: 10.21668/health.risk/2023.4.01.eng
  2. Bibitova Sh.S., Galiakparova Zh.Zh., Zhaksylyk M.A., Lopuha I.V., Oralova R.N., Sandybayeva A.K., Khashimov Zh.U., Dyussembaeva N.K. [et al.]. Lost years of life due to the mortality from diseases of the urinary system in the industrial region of Kazakhstan with air pollution. Gigiena i sanitariya, 2024, vol. 103, no. 2, pp. 120–129. DOI: 10.47470/0016-9900-2024-103-2-120-129 (in Russian)
  3. Mozganov M.Yu., Nikolaeva N.I., Filin A.S., Malyshek V.V., Onishchenko G.G. Analysis of some promising direc-tions of the development of the public health risk assessment in the Russian Federation (review article). Gigiena i sanitariya, 2024, vol. 103, no. 1, pp. 76–80. DOI: 10.47470/0016-9900-2024-103-1-76-80 (in Russian)
  4. Rakitskii V.N., Kuz'min S.V., Avaliani S.L., Shashina T.A., Dodina N.S., Kislitsin V.A. Contemporary challenges and ways to improve health risk assessment and management. Health Risk Analysis, 2020, no. 3, pp. 23–29. DOI: 10.21668/health.risk/2020.3.03.eng
  5. Zemlyanova M.A., Zaytseva N.V., Kiryanov D.A., Ustinova O.Yu. Methodological approaches to evaluation and pre-diction of individual risk to health under the exposure to a complex of different factors for tasks of personalized prophylaxis. Gigiena i sanitariya, 2018, vol. 97, no. 1, pp. 34–43. DOI: 10.18821/0016-9900-2018-97-1-34-43 (in Russian).
  6. Vasilieva T.P., Larionov A.V., Russkikh S.V., Zudin A.B., Gorenkov R.V., Vasiliev M.D., Kostrov A.A., Khapalov A.A. Methodological Approach to Organizing Public Health Monitoring in the Russian Federation. ZNiSO, 2022, no. 7, pp. 7–17. DOI: 10.35627/2219-5238/2022-30-7-7-17 (in Russian).
  7. Vasilieva T.P., Larionov A.V., Russkikh S.V., Zudin A.B., Vasyunina A.E., Vasiliev M.D., Rotov V.M. Methodologi-cal Approach to Compiling a Classifier of Public Health Challenges. ZNiSO, 2024, vol. 32, no. 2. pp. 7–17. DOI: 10.35627/2219-5238/2024-32-2-7-17 (in Russian).
  8. Zaitseva N.V., Popova A.Yu., Kleyn S.V., Letyushev A.N., Kiryanov D.A., Chigvintsev V.M., Glukhikh M.V. Modi-fying impact of environmental factors on the course of an epidemic process. Gigiena i sanitariya, 2022, vol. 101, no. 11, pp. 1274–1282. DOI: 10.47470/0016-9900-2022-101-11-1274-1282 (in Russian).
  9. Prognoz nauchno-tekhnologicheskogo razvitiya Rossii: 2030. Meditsina i zdravookhranenie [Forecast of scientific and technological development of Russia: 2030. Medicine and healthcare]. In: L.M. Gokhberg, L.M. Ogorodova eds. Moscow, Min-istry of Education and Science of the Russian Federation, HSE University, 2014, 48 p. (in Russian).
  10. Skinner M.K. Environmental epigenomics and disease susceptibility. EMBO Rep., 2011, vol. 12, no. 7, pp. 620–622. DOI: 10.1038/embor.2011.125
  11. Rappaport S.M. Discovering environmental causes of disease. J. Epidemiol. Community Health, 2012, vol. 66, no. 2, pp. 99–102. DOI: 10.1136/jech-2011-200726
  12. Zaitseva N.V., Zemlianova M.A., Dolgikh O.V. Genomic, transcriptomic and proteomic technologies as a modern tool for health disorders diagnostics, associated with the impact of environmental factors. Gigiena i sanitariya, 2020, vol. 99, no. 1, pp. 6–12. DOI: 10.47470/0016-9900-2020-99-1-6-12 (in Russian).
  13. Anderson N.L., Anderson N.G. The human plasma proteome: history, character, and diagnostic prospects. Mol. Cell. Proteomics, 2002, vol. 1, no. 11, pp. 845–867. DOI: 10.1074/mcp.r200007-mcp200
  14. Corzett T.H., Fodor I.K., Choi M.W., Walsworth V.L., Turteltaub K.W., McCutchen-Maloney S.L., Chromy B.A. Statistical analysis of variation in the human plasma proteome. J. Biomed. Biotechnol., 2010, vol. 2010, pp. 258494. DOI: 10.1155/2010/258494
  15. Ahmad A., Imran M., Ahsan H. Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detec-tion, Analysis, and Validation of Novel Biomarkers of Diseases. Pharmaceutics, 2023, vol. 15, no. 6, pp. 1630. DOI: 10.3390/pharmaceutics15061630
  16. Zaitseva N.V., May I.V., Kiryanov D.A., Goryaev D.V., Kleyn S.V. Social and hygienic monitoring today: state and prospects in conjunction with the risk-based supervision. Health Risk Analysis, 2016, no. 4, pp. 4–16. DOI: 10.21668/health.risk/2016.4.01.eng
  17. Agamagomedova S.A. Risk-Oriented Approach in the Implementation of Control and Supervision Activities: Theo-retical Justification and Problems of Application. Sibirskoe yuridicheskoe obozrenie, 2021, vol. 18, no. 4, pp. 460–470. DOI: 10.19073/2658-7602-2021-18-4-460-470 (in Russian).
  18. Cooke A.L., Morris J., Melchior J.T., Street S.E., Jerome W.G., Huang R., Herr A.B., Smith L.E. [et al.]. A thumbwheel mechanism for APOA1 activation of LCAT activity in HDL. J. Lipid Res., 2018, vol. 59, no. 7, pp. 1244–1255. DOI: 10.1194/jlr.M085332
  19. Guo Q., Zhang C., Wang Y. Overexpression of apolipoprotein A-I alleviates endoplasmic reticulum stress in hepato-cytes. Lipids Health Dis., 2017, vol. 16, no. 1, pp. 105. DOI: 10.1186/s12944-017-0497-3
  20. Gharibyan A.L., Wasana Jayaweera S., Lehmann M., Anan I., Olofsson A. Endogenous Human Proteins Interfering with Amyloid Formation. Biomolecules, 2022, vol. 12, no. 3, pp. 446. DOI: 10.3390/biom12030446
  21. Liz M.A., Gomes C.M., Saraiva M.J., Sousa M.M. ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity. J. Lipid Res., 2007, vol. 48, no. 11, pp. 2385–2395. DOI: 10.1194/jlr.m700158-jlr200
  22. Magalhães J., Eira J., Liz M.A. The role of transthyretin in cell biology: impact on human pathophysiology. Cell. Mol. Life Sci., 2021, vol. 78, no. 17–18, pp. 6105–6117. DOI: 10.1007/s00018-021-03899-3
  23. Kim S.Y., Park S.C. Physiological antioxidative network of the bilirubin system in aging and age-related diseases. Front. Pharmacol., 2012, vol. 3, pp. 45. DOI: 10.3389/fphar.2012.00045
  24. Wang D., Tosevska A., Heiß E.H., Ladurner A., Mölzer C., Wallnerv M., Bulmer A., Wagner K.-H. [et al.]. Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression. J. Am. Heart Assoc., 2017, vol. 6, no. 5, pp. e005520. DOI: 10.1161/JAHA.117.005520
Received: 
03.05.2024
Approved: 
07.06.2024
Accepted for publication: 
20.06.2024

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