Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices

The addition of a new compound containing platinum, 254-S, an antineoplastic agent, to medium had no effect on p-aminohippurate (PAH) accumulation, gluconeogenesis, or potassium and ATP concentrations in rat kidney cortical slices at the concentrations tested, up to 10 mM. At 1 mM, cisplatin, used for comparison, significantly decreased all of these biochemical indices in the slices. Administration of 254-S at a low dose (10 mg/kg i.v.) to rats decreased the ability of the slices to accumulate PAH and to maintain the potassium concentration, without affecting levels of urea or creatinine in blood plasma. 254-S at a high dose (20 mg/kg i.v.) or cisplatin at 5 mg/kg (i.v.) also decreased these indices in the slices, and affected urea and creatinine in blood plasma. These results suggested that use of the renal slice technique gives data useful for the evaluation of the nephrotoxicity of 254-S, and that PAH accumulation and the potassium concentration in slices from rats treated with 254-S are indicators of nephrotoxic damage.