Biochemical disturbances as precursors of structural changes in Al(OH)₃-induced nephrotoxicity in a subchronic animal experiment

Aluminum is a cumulatively widespread man-made pollutant. The kidneys play a key role in the excretion of aluminum, but information on the subchronic effect of low doses of the pollutant on the target organ is limited. This study aimed to investigate the relationship between functional and structural changes in the kidneys of experimental animals with prolonged oral administration of aluminum hydroxide (Al(OH)₃). The experiment involved 48 rats divided into control and three experimental groups that received Al(OH)₃ orally at doses of 0,015, 0,15, and 1,5 mg/kg/day for 60 days. Biochemical parameters of blood serum and histological structure of the kidneys were assessed. A dose-dependent decrease in uric acid was revealed, with minimal values at a dose of 0.015 mg/kg (40.06±4.02 μmol/l versus 85.60±5.48 μmol/l in the control; p<0.05). The urea concentration also decreased significantly (p=0.001) and dose-dependently in all experimental groups. The creatinine level remained unchanged without statistically significant. Histological analysis showed the preservation of the normal structure of nephrons; however, in the groups of animals receiving the pollutant at doses of 0.15 and 1.5 mg/kg, a focal tendency towards an increase in glomerular cellularity was noted, which may indicate initial signs of damage. Subchronic oral administration of Al(OH)₃ resulted in dose-dependent biochemical changes indicating dysregulation of antioxidant defense and nitrogen metabolism, in the absence of pronounced morphological changes in the kidneys of experimental animals. The observed functional impairments preceded structural damage, confirming the importance of biochemical markers for the early diagnosis of aluminum-induced nephrotoxicity.