In vitro assessment of cephaloridine nephrotoxicity: comparison of renal cortical slice and renal tubule fragment techniques.
Renal cortical slices and a suspension of renal tubule fragments were prepared from male Wistar rats that had received a single s.c. dose of either cephaloridine (100 mg/kg) or normal saline (1 ml/kg) 48 h previously. The comparative sensitivity of these tissue preparations as in vitro models to assess nephrotoxin-induced changes in renal function was investigated by measuring the ability of the preparations to undertake the active accumulation of [3H]para-aminohippuric acid and to undertake gluconeogenesis from sodium pyruvate. Through the use of the cortical slice technique, [3H]para-aminohippuric acid tissue accumulation and glucose production in the cephaloridine-treated group were not significantly different from control. In contrast, using the tubule fragment technique, significant (p less than 0.05) reductions in the accumulation of [3H]para-aminohippuric acid and in the production of glucose via gluconeogenesis, between cephaloridine and normal saline control treatments were observed. Control values in the tubule fragment technique, for para-aminohippuric acid transport and glucose production via gluconeogenesis, were observed to be much greater than control values obtained from the cortical slice technique. It is suggested that the tubule fragment technique may be a more valuable in vitro preparation to assess the effects of potential nephrotoxins on tubule transport function than the still widely used cortical slice technique. The use of specific metabolic substrates, such as acetate, that will stimulate cellular metabolism and substrate transport, will also enhance the value of the technique.
Cruz
R H
RH
Welsh School of Pharmacy, UWIST, Cardiff, Wales, UK.
Gumbleton
M
M
Nicholls
P J
PJ
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D002509:Cephaloridine / Q000633:toxicity*; D005943:Gluconeogenesis / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D002509:Cephaloridine; D010130:p-Aminohippuric Acid