Histopathological and immunohistochemical evaluation of renal tissue in rats following chronic low-dose cadmium exposure and the nephroprotective potential of N-acetylcysteine, Гістопатологічна та імуногістохімічна оцінка тканини нирок щурів за хронічного впливу низьких доз кадмію та нефропротекторний потенціал N-ацетилцистеїну

<jats:p>Cadmium is a nephrotoxic heavy metal that progressively accumulates within renal tissue, inducing structural injury. This study evaluated the histopathological, morphometric, and immunohistochemical effects of chronic low-dose cadmium exposure on rat kidneys and investigated the nephroprotective potential of N-acetylcysteine. Thirty adult male Sprague-Dawley rats were divided into three groups: control; cadmium chloride (0.5 mg/kg orally twice weekly for eight weeks); and cadmium chloride concurrently with N-acetylcysteine (150 mg/kg/day intraperitoneally). Renal sections were processed for hematoxylin-eosin, Periodic Acid–Schiff, and Masson’s trichrome staining, and for immunohistochemical localization of Caspase-3 and Ki-67. Quantitative morphometric analysis demonstrated that chronic cadmium exposure increased the kidney-to-body weight ratio by 29.6 %, reduced mean glomerular diameter by 22 % (82.4±3.1 versus 105.6±4.2 micrometers; p=0.004), caused a 38 % decrease in tubular lumen area (p&lt;0.001), and triggered a 4.1-fold expansion of interstitial fibrosis (15.8 ± 1.2% versus 3.9±0.5 %; p=0.001). Immunohistochemical data revealed that cadmium provoked a 3.2-fold elevation in Caspase-3 expression (18.2±2.1 % versus 5.6±1.0 %; p=0.002) and a 45% suppression of the Ki-67 proliferative labeling index (9.3±1.4 % versus 17.0±1.8 %; p=0.008), indicating accelerated apoptosis and compromised regeneration. A strong positive correlation was identified between interstitial fibrosis and Caspase-3 expression (Pearson r = 0.89, p&lt;0.001). Co-administration of N-acetylcysteine significantly attenuated these alterations: interstitial fibrosis was reduced by 62% (6.7±0.9 %; p=0.003), mean glomerular diameter was partially restored to 96.1±3.8 micrometers, tubular lumen area recovered to 61.2±2.9 % (p=0.02), Caspase-3 expression decreased to 8.3±1.2 % (p=0.01), and the Ki-67 labeling index rose to 13.5±1.3 % (p=0.04). Collectively, these findings prove that chronic cadmium exposure induces apoptosis-driven fibrosis, whereas N-acetylcysteine provides substantial nephroprotection by suppressing cell death, preventing fibrosis, and partial restoring proliferative capacity.</jats:p>