Dose-dependent morphological and molecular genetic changes in rat kidneys during chronic exposure to aluminum hydroxide

Aluminum is one of the most abundant elements in the Earth’s crust and is widely used in industry, domestic applications, and medicine. Despite its extensive utilization, its potential toxicity remains a subject of active scientific debate and investigation. The main routes of aluminum entry into the human body include food, drinking water, inhaled air, and pharmaceutical products, all of which contribute to its accumulation in biological tissues and increase the risk of chronic intoxication. Vulnerable populations include children and individuals with impaired renal function, particularly those with chronic kidney disease. The aim of this study was to evaluate the effects of chronic exposure to aluminum hydroxide on kidney morphology and the expression of Mt1a, Mt2a, and Mt3a genes in rats, with an emphasis on identifying dose-dependent effects and elucidating possible mechanisms of nephrotoxicity. The experiment was conducted on 40 female white rats randomly assigned to one control and four experimental groups (8 animals each). Over the course of four months, the experimental groups received aluminum hydroxide orally in varying doses. Toxicity assessment included quantitative real-time PCR analysis of gene expression and histological examination of renal tissue. Significant upregulation of Mt2a and Mt3a was observed at higher aluminum doses (p < 0.001), while Mt1a expression demonstrated high interindividual variability. Histopathological evaluation revealed signs of interstitial inflammation, fibrosis, and chronic glomerulonephritis. Chronic exposure to aluminum hydroxide induces pronounced dosedependent morphological and molecular changes in the kidney. The Mt2a and Mt3a genes may serve as promising molecular biomarkers of aluminum-associated nephrotoxicity.

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