Forecast of probable negative effects initiated by transformation of the proteomic profile of human blood plasma under combined exposure to chemicals

Introduction. The study of the mechanisms of external environmental effects of chemicals on the human body using highly informative proteomic profiling technologies makes it possible to predict the development of negative effects at the earliest stage of their formation. In combination with experimental studies that exclude the influence of interfering factors, the accuracy of identifying changes in the protein profile increases. Assessing the cause-and-effect relationships between exposure to chemicals and protein transformation increases the effectiveness of prognosis and measures to prevent negative consequences.

The purpose of the work is the forecast of probable negative effects initiated by the transformation of the proteomic profile of blood plasma under the combined influence of chemicals, relied upon on bioinformation matrices based on the results of a comparative analysis of natural and experimental studies (using the example of aluminum oxide, hydrogen fluoride, and benzo(a)pyrene).

Materials and methods. Using the methods of chemical-analytical, statistical, proteomic, and bioinformational analysis, molecular-cellular events were identified in 4–7 years children exposed to aerogenic exposure to benzo(a)pyrene, hydrogen fluoride, and aluminum oxide (field studies). During the comparative analysis, the obtained results were verified by data from experimental studies (Wistar rats) subjected to combined and isolated inhalation exposure in doses equivalent to real ones. Identical proteins were identified and a bioinformation matrix was constructed, on the basis of which a forecast of probable negative effects was made using generally accepted metadata databases.

Results. As a result of field studies, in children exposed to benzo(a)pyrene at a level of up to 2.2 MPC.g. (up to 2.2 RfC), aluminum oxide and hydrogen fluoride — up to 0.3 MPC.g. (up to 0.1 RfC), the concentrations of the studied substances in biological media were established to be 2.0–3.6 times higher than the comparison indicators and reference levels. In the experiment, the content of these contaminants in biological media in exposed animals was up to 19.4 times higher than in the control. In children there were identified, 22 proteins corresponding to the library mass spectra, 40 proteins — in animals. In a comparative analysis of proteins identified in the blood plasma in children and rats, Apolipoprotein A-I and Transthyretin were identified and assessed as “identical”. The expression of these proteins elevates with increasing concentration of the studied substances in biological media. According to information from databases, increased expression of Apolipoprotein A-I and Transthyretin signals an higher risk for the oxidative stress, impaired lipid metabolism, and the development of inflammatory processes. The constructed bioinformation matrix made it possible to predict metabolic disorders, mainly in the tissues of the nervous and hepatobiliary systems.

Limitations. The study does not allow drawing definitive conclusions about the effect of the studied chemicals on changes in the expression of proteins and the genes encoding them, since in this work only the aerogenic route of entry is considered.

Conclusion. The transformation of the proteomic profile of blood plasma was established in field studies and experimentally verified during chronic inhalation exposure to aluminum oxide, hydrogen fluoride and benzo(a)pyrene. A comparative analysis of the identified proteins revealed two identical ones — Apolipoprotein A-I and Transthyretin. A bioinformation matrix was constructed and a forecast was made for the development of negative effects in the form of activation of oxidative processes, lipid dysmetabolism and inflammation, the metabolic pathway of which is associated with changes in the expression of these proteins. In the absence of preventive measures, this can lead to the development of atherosclerosis, hypertension, obesity, amyloidosis, hyperthyroidism, etc. in older age. The use of structural bioinformation matrices as a forecasting tool in hygienic research increases the effectiveness of targeted prevention measures for negative consequences due to environmental exposure to chemicals.

Compliance with ethical standards. Experimental studies on a biological model were conducted in compliance with the requirements of the European Convention for the Protection of Vertebrates Used for Experimental or Other Scientific Purposes (ETS No. 123). The examination of children was carried out in compliance with the ethical principles of the Helsinki Declaration (2013). The research was approved by the Committee on Biomedical Ethics of the Federal State Budgetary Institution “FNC MPT URZN” (minutes of meeting No. 1 dated 02/14/2021).

Contribution:
Zaitseva N.V. — editing;
Zemlyanova M.A. — concept and design of research, editing;
Peskova E.V. — concept and design of research, collection of literature data, statistical processing of material, writing of text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest in connection with the publication of this article.

Acknowledgement. The study was carried out at the expense of the Federal budget.

Received: February 16, 2024 / Revised: March 13, 2024 / Accepted: April 9, 2024 / Published: June 17, 2024