Comparison of the toxicities of cisplatin and a new cisplatin-procaine complex to rat renal cortical slices

1 Procaine has previously been shown to diminish the nephrotoxicity of cisplatin and the nephrotoxic effects of cisplatin and a new cisplatin complex (cis-diammine chloro - [2 - (diethylamino) ethyl - 4 - aminobenzoate, N4]- chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were com pared with rat renal cortical slices.2 Cisplatin at 1 mM caused toxicity to the slices, as shown by an increase in the leakage of aspartate aminotransfer ase and lactate dehydrogenase from the slices into the incubation medium and a decrease in the reduction of a tetrazolium dye (MTT assay). Addition of procaine (1 mM) protected against cisplatin-induced toxicity. DPR either at 1 mM or at 4 mM had no effect either on the enzyme leakage or MTT reduction by the renal slices, but DPR at 10 mM produced a similar magnitude of enzyme leakage to cisplatin (1 mM).3 DPR lowered the concentration of ATP and glutathione (GSH) in the slices but was less potent than cisplatin. Thiobarbituric ac...