The impact of chronic stress on the nephrotoxic effect of paracetamol: histomorphological and biochemical analysis

Chronic stress and paracetamol use are common factors that potentially disrupt homeostasis. Their interaction and impact on renal function still remain poorly understood. Objective: The aim of the study is to evaluate the effect of chronic stress on paracetamol nephrotoxicity in rats using histomorphological and biochemical analysis. Materials and Methods. Forty-eight rats were divided into four groups: control, stress, paracetamol (1000 mg/kg/day), and paracetamol + stress. Chronic stress was modeled over a period of 28 days. After euthanasia, the authors performed histological analysis of the kidneys (H&E staining), and measured serum biochemical parameters (enzymes, nitrogen metabolites, lipids) were. Statistical analysis was carried out using the bootstrap test with the Holm-Bonferroni correction (p<0.05). Results. The most pronounced changes in nitrogen metabolism were revealed under combined effect: in males in the “Paracetamol + stress” group, urea and uric acid levels were at their maximum and significantly exceeded the control parameters (11.47±0.36 mmol/L versus 9.81±0.22 mmol/L and 86.86±4.37 μmol/L versus 55.50±2.28 μmol/L, p=0.001). Histologically, this group demonstrated the most severe lesions: deformation of renal corpuscles, foci of sclerosis, massive accumulations of erythrocytes. Significant sex differences were revealed: paracetamol increased the triglyceride levels in females (2.28±0.41 mmol/L vs. 0.97±0.06 mmol/L, p=0.007), but decreased them in males. Chronic stress caused a significant increase in LDH activity in males (2265.69±86.57 U/L vs. 1777.02±93.94 U/L, p=0.001). Conclusion. A synergistic effect of chronic stress and paracetamol was established, leading to significant nitrogen metabolism disorders and progressive structural damage to the kidneys. The results demonstrate a pronounced sex-specificity of metabolic reactions. These findings indicate a potential risk of increased paracetamol nephrotoxicity under chronic stress and necessitate further research in this area.