A single dose of puromycin aminonucleoside (PAN) given parenterally to rats
induces ultrastructural glomerular changes and a nephrotic syndrome simila
r in many respects to human minimal change nephropathy. The exact aetiologi
es of both the human and the experimental syndromes are unknown, and are pr
obably multifactorial. However, among the observed consequences in humans a
nd rats is increased plasma protein excretion in urine, beginning in the la
tter typically 3-6 days after PAN administration. In view of this, two-dime
nsional polyacrylamide gel electrophoresis (2-D PAGE) has been used to prof
ile urinary proteins during PAN-induced nephrotoxicity and subsequent recov
ery in the rat. In addition, urinary high performance liquid chromatography
(HPLC) profiles and high resolution proton nuclear magnetic resonance (NMR
) spectroscopy has been utilised to simultaneously detect toxin-induced cha
nges in the relative concentrations of a number of metabolites. The proteom
ic approach, in conjunction with these other techniques, has the potential
to provide significantly more mechanistic information than is provided read
ily by traditional clinical chemistry.