Biochemical characterisation of para-aminophenol-induced nephrotoxic lesions in the F344 rat.
The acute biochemical effects of the nephrotoxin p-aminophenol (PAP) were studied in detail using a combination of conventional bioanalytical and 1H-NMR spectroscopic methods. Dosing PAP (25-100 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy with consequent elevations in urinary enzymes, glucose, and urine total protein as shown by conventional methodology. 1H-NMR spectroscopy at 400 MHz of urine from PAP-treated rats also revealed a characteristic glycosuria, with concomitant amino aciduria. The increased excretion of these compounds indicates functional defects in the proximal tubule and reduced solute reabsorption efficiency. In addition, 1H-NMR urinalysis and conventional enzymatic analysis showed a dose-related lactic aciduria. Other changes detected by 1H-NMR included a dose-related reduction in the excretion of citrate (confirmed by a conventional biochemical method) and an increase in the excretion of acetate. The degree of abnormalities shown by 1H-NMR urinalysis agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity. 1H-NMR urinalysis therefore serves to highlight changes in the excretion of low MW urine components not routinely studied by conventional biochemical analysis.
Gartland
K P
KP
Department of Chemistry, Birkbeck College, University of London, UK.
Bonner
F W
FW
Timbrell
J A
JA
Nicholson
J K
JK
D000596:Amino Acids / Q000652:urine; D000627:Aminophenols / Q000633:toxicity*; D000818:Animals; D002951:Citrates / Q000652:urine; D006029:Glycosuria / Q000139:chemically induced / Q000652:urine; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007773:Lactates / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014508:Urea / Q000652:urine
D000596:Amino Acids; D000627:Aminophenols; D002951:Citrates; D007773:Lactates; D014508:Urea; C026729:4-aminophenol