The effect of aluminum hydroxide on the formation of nephrotoxic effects in rats under oral administration

Introduction. Heavy metals are among the most dangerous environmental pollutants primarily due to their ability to bioaccumulate and high toxicity even in low concentrations. The aim of the study was to investigate the nephrotoxic effect of aluminum upon oral administration of aluminum hydroxide to rats in various doses under subchronic experimental conditions.Materials and methods. The study was conducted on white outbred rats of both sexes. Animals were randomly divided into 4 groups: control group (C) and 3 experimental groups. To assess the toxic effect of the metal, animals of the 1st, 2nd, and 3rd experimental groups were administered aluminum hydroxide solution orally in three working doses 5 times a week for 2 months. Total RNA isolated from kidney tissue samples was used for genetic studies. Gene expression analysis was performed by real-time PCR using oligonucleotide-specific primers in the presence of the intercalating dye SYBR Green. Biochemical and histological analysis was performed using standard methods.Results. As a result, biochemical parameters did not demonstrate a picture characteristic of kidney damage. Histological analysis also did not reveal pronounced dystrophic and necrotic changes in the renal structures after 2 months of intoxication. However, the analysis of the expression fold of the MT1a и Mt2a genes established the expected gain in the transcriptional activity of genes in response to the introduction of aluminum hydroxide. The expression of the Mt1a gene was increased by 1.5 times relative to the control in the group with the maximum dose of the toxicant. Whereas the expression of the Mt2a gene showed greater sensitivity and demonstrated a 1.4-fold increase already at a dose of 0.015 mg/kg, and at the maximum dose it exceeded the control values ​​by 2.5 times.Limitations. The study was performed on a limited number of animals of one biological species.Conclusion. The obtained results allow considering the expression of metallothionein genes as a more sensitive and earlier indicator of metal intoxication compared to classical diagnostic methods.Compliance with ethical standards. The study was approved by the local ethics committee of the Ufa Research Institute of Occupational Medicine and Human Ecology (minutes of the meeting No. 01-02 dated 08.02.2024), conducted in accordance with the generally accepted scientific principles of the Helsinki Declaration of the World Medical Association (2013 edition).Contribution: Valova Ya.V. — concept and design of the study, collection and processing of data, statistical processing, writing the text; Gizatullina A.A., Ryabova Yu.V., Karimov D.D., Akhmadeev A.R., Smolyankin D.A. — collection of data and data processing;Repina E.F. — editing; Kudoyarov E.R. — statistical 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.Funding. Industry research program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing for 2021-2025 “Scientific substantiation 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”, on the topic: “Experimental substantiation of highly sensitive markers of the impact of toxic metals on the body and the development of preventive measures” No. NIOKTR I124021200153-3Received: January 31, 2025 / Accepted: March 26, 2025 / Published: June 27, 2025

heavy metals, metallothioneins, aluminum hydroxide, subchronic intoxication, gene expression, nephrotoxicity