Renal cytotoxicity of cisplatin in cultured glomerular mesangial and proximal and distal tubular cells.
Cisplatin is of considerable therapeutic value owing to its anti-tumoral activity. Unfortunately, its nephrotoxicity can reduce its clinical use. In vivo toxicity studies have shown large renal haemodynamic changes and differential tubular nephrotoxicity with strong proximal tropism. The present study compared renal cytotoxicity of cisplatin in three different cell cultures: glomerular mesangial cells and two renal tubular cell lines, LLCPK(1) (proximal) and MDCK (distal). Cell viability was assessed by the neutral red test. Cisplatin at 10(-4)m induced a similar cell mortality in the three targets (about 80%). Mesangial cell mortality was concentration dependent, at 82, 31, 19 and 12% for 10(-4)-10(-7)m, respectively. The IC(50) for MDCK cells was 5.35 x 10(-5)m compared with 3.25 x 10(-5)m for LLCPK(1). For the different cisplatin concentrations mortality was two to three times higher in LLCPK(1), confirming the strong proximal tropism of cisplatin. These results demonstrate cisplatin cytotoxicity at both the glomerular and tubular levels, and open the way for comparative studies with new cisplatin derivatives for the optimization of their clinical use.
Delbancut
A
A
Department of Cell Biology, Faculty of Pharmacy, 3 Place de la Victoire, 33000 Bordeaux, France.
Lagroye
I
I
Cambar
J
J