Evaluation of apoptosis gene expression and morphological changes in kidney tissue under acrylamide exposure and prophylactic drug correction

Introduction. Acrylamide is a well-known toxicant, contact with which occurs both in industrial and domestic conditions. It has been found to have nephrotoxic properties.

The purpose of the work is to evaluate the expression of the Casp7, Chek1 genes and changes in the structure of the kidney tissue in rats under long-term exposure to acrylamide and preventive correction.

Materials and methods. The experiment used sixty white outbred male rats. Acrylamide was administered intragastrically at a dose of 5 mg/kg body weight for 90 days. Correction of possible violations was carried out 1 hour before the administration of the toxicant with complex compounds of hydroxymethyluracil. Gene expression was studied using real-time PCR. SPSS Statistics 21.0 software (IBM, USA) was used for statistical data analysis. Morphological studies of the structure of rat kidneys were carried out using standard methods.

Results. Studies have shown that exposure to acrylamide for 3 months at a dose of 5 mg/kg body weight causes structural changes in the kidney tissue in rats. With long-term exposure to acrylamide, there is a tendency to increase the expression of the Chek1 and Casp7 genes, which may indicate cell damage and activation of repair and apoptosis processes in them. The combination of hydroxymethyluracil with acetylcysteine had the greatest protective effect on the structure of the kidneys and the expression of the Casp7 gene.

Limitations are that morphological changes in kidney tissue during long-term exposure to acrylamide were correlated with the expression of only two apoptotic genes. For a more complete understanding of the pathogenetic changes during the damaging effect of acrylamide on the kidneys, it is necessary to conduct a multivariate analysis taking into account other toxicological and genetic indicators.

Conclusion. Acrylamide, when ingested for a long time at a dose of 5 mg/kg body weight, has a nephrotoxic effect, which is confirmed by data from morphological studies and a tendency to increase the expression of the main apoptosis genes in kidney tissue. The best protective effect according to the studied parameters was observed with the prophylactic administration of a complex compound of hydroxymethyluracil with acetylcysteine.

Compliance with ethical standards. the study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (the meeting report No. 01–03 dated 03.05.2024), conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experiments or for Other Scientific Purposes (ETS N 123), Directive of the European Parliament and the Council of the European Union 2010/63/EC of 22.09.2010 on the protection of animals used for scientific purposes.

Contributions:
Repina E.F. – study concept and design, statistical analysis, text writing;
Karimov D.O. – concept and design of the study, writing the text;
Baygildin S.S. – data collection and processing, text writing;
Shaykhlislamova E.R. – editing;
Bakirov A.B. – concept and design of the study;
Gimadieva A.R. – synthesis of hydroxymethyluracil complex compounds;
Yakupova T.G., Khusnutdinova N.Yu., Smolyankin D.A. – data collection and processing.
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 no conflict of interest.

Acknowledgement. The work was carried out as part of the state assignment for the industry research program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing “Scientific justification of the national system for ensuring sanitary and epidemiological well-being, managing health risks and improving the quality of life of the population of Russia” for 2021-2025. clause 6.1.8, state no. registration 121062100058-8.

Received: March 29, 2024 / Accepted: June 19, 2024 / Published: January 31, 2025