CHRONIC HEAVY METAL-CONTAMINATED FEED EXPOSURE AND PROGRESSIVE RENAL DYSFUNCTION IN WISTAR RATS

Heavy metals released into the environment can accumulate in soil and plants and subsequently enter animal diets. The renal consequences of prolonged exposure to mixed metal contaminants require integrated functional and morphological assessment. Objective: To examine changes in kidney function and histopathology during 16 weeks of exposure to heavy metal-contaminated feed in Wistar rats. Methods: Male Wistar rats received contaminated feed daily for 16 weeks. Feed contamination was assessed by inductively coupled plasma mass spectrometry (ICP-MS; Agilent 7900). Serum creatinine and urea, glomerular filtration rate estimated from endogenous creatinine clearance, fractional excretion of sodium (FENa), and renal histopathology were assessed. Results: Serum creatinine increased from approximately 62 μmol/L at week 1 to 77 μmol/L by week 11 (control, 59 μmol/L). Urea increased from approximately 14 mmol/L at week 1 to 18 mmol/L at week 16 (control, 12 mmol/L). Creatinine clearance decreased from 259 to 198 μL/min over the observation period (control, 281 μL/min). FENa increased from 0.76% at week 1 to 0.83% at week 12, with a further modest increase thereafter. Histopathological observations included tubular epithelial injury, glomerular alterations, inflammatory changes, hemorrhage, necrosis, and fibrosis. Conclusions: Prolonged dietary exposure to heavy metal contaminants was associated with progressive renal functional impairment and structural injury. These observations support combined biochemical, clearance-based and histological evaluation of mixed-metal nephrotoxicity.