Evaluation of renal enzymuria and cellular excretion as an marker of acute nephrotoxicity due to an overdose of paracetamol in Wistar rats.
BACKGROUND
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 T(0) 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.


CONCLUSIONS
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.
da Silva Melo
Denizar Alberto
DA
Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Rio Grande do Sul, Brazil.
Saciura
Vasyl Custódio
VC
Poloni
Jose Antonio Tesser
JA
Oliveira
Carmem Silvana Araújo
CS
Filho
José Carlos Farias Alves
JC
Padilha
Rossali Zingano
RZ
Reichel
Carlos Luis
CL
Neto
Emilio Jeckel
EJ
Oliveira
Raquel Mattos
RM
D'avila
Luiz Cláudio
LC
Kessler
Adriana
A
de Oliveira
Jarbas Rodrigues
JR
D000082:Acetaminophen / Q000633:toxicity*; D000208:Acute Disease; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000187:drug effects / Q000652:urine; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000652:urine; D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000652:urine; D015415:Biomarkers / Q000652:urine; D062787:Drug Overdose; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology* / Q000652:urine; D007677:Kidney Function Tests; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000652:urine; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000652:urine
D015415:Biomarkers; D000082:Acetaminophen; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase