Hepatotoxicity of cadmium at long-term exposure

Introduction. Cadmium poses a serious threat to human health. The main target organs in cadmium intoxication are the liver, kidneys, and skeletal system. Cadmium damages the antioxidant system and induces the development of oxidative stress, leading to structural and metabolic changes in the liver. Understanding the molecular mechanisms underlying liver diseases can help in the development of strategies for establishing markers for their accurate and timely diagnosis.The aim of the work is to assess the degree of hepatotoxicity of various doses of cadmium during long-term exposure based on morphological and biochemical indices.Materials and methods. The studies were conducted on outbred male rats. For six months, rats were intragastrically administered an aqueous solution of Cd chloride in doses from 0.001 to 1.0 mg / kg b.w. Morphological studies of the liver structure were carried out. Lipid metabolism indices (triglycerides and cholesterol) were studied. Dose-response curves were constructed.Results. The studies showed cadmium, when administered over a long period of time, to have a significant toxic effect on the liver structure. The slope of the dose-response curve obtained for the TG level has a more pronounced curvature than the slope of the curve for the serum HCT level. A high slope indicates that small changes in the dose lead to significant changes in the effect.Limitations. For an objective assessment of cadmium hepatotoxicity under long-term exposure to different doses, it is necessary to take into account the degree of change in a large number of biochemical indices, as well as perform morphometric studies of the liver tissue.Conclusion. With prolonged administration to laboratory animals at doses from 0.001 to 1.0 mg/kg b.w., cadmium has a pronounced dose-dependent hepatotoxic effect, characterized by disturbances in lipid metabolism (dyslipidemia) and changes in liver structure.Compliance with ethical standards. The study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (meeting minutes No. 01-10, 10/09/2024), 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: Khmel A.O. – data processing, text writing; Repina E.F., Ryabova Yu.V. – text writing, editing; Karimov D.O., Valova Y.V. – concept and design of the study; Smolyankin D.A., Baygildin S.S., Akhmadeev A.R. – collection and processing of data. 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. 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 (Rospotrebnadzor) “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 6.1.9, state no. registration 121062100057-1.Received: December 4, 2024 / Accepted: March 26, 2025 / Published: June 27, 2025

cadmium chloride, rats, experiment, long-term exposure, liver, morphology, cholesterol, triglycerides