Evaluation of renal enzymuria and cellular excretion as an marker of acute nephrotoxicity due to an overdose of paracetamol in Wistar rats

Introduction: The present study was conducted to determine whether the urinary levels of excreted enzymes, gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate (AST) and alanine aminotransferases (ALT), can efficiently indicate, within 24 h, an acute nephrotoxicity due to an overdose of paracetamol (PAR). Methods: A baseline urine was collected from the experimental group. Thereafter, blood collected from the orbital sinus (1.0 ml) and paracetamol (650 mg/kg of body weight) was administered by gavage. After the drug administration, animals were returned to the metabolic cages and then urine was collected in the next 22 h. Blood and urine collection was performed at time 0 + 24 h (T-24), as well as at times 48 and 72 h (T-48 and T-72). After the last urine and blood collection, the rats were killed and the kidneys removed and prepared for histological examination. Plasma creatinine and urinary levels of creatinine (to determinate glomerular filtration rate-GFR), GGT, ALP, LDH, ALT and AST were measured. Kidney tissues were stained with hematoxylin and eosin stain for histological assessment. Results: Urinary levels of GGT, ALP and LDH enzymes were significantly higher (P < 0.05) at T-24 when compared to the levels at To and returned to basal levels at T-48 and T-72. The number of urinary epithelial cells at T-24 was significantly higher when compared to the control time (T-0) (P < 0.001). The GFR was significantly reduced 24, 48 and 72 h after the drug administration. Conclusion: The number of urinary epithelial cells and urinary enzymes levels are a simple and low cost procedure that is available and can help in the detection of renal acute lesions. (c) 2006 Elsevier B.V. All rights reserved.