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 cisplati n complex (cis-diamminechloro- [2-(diethylamino) ethyl-4-aminobenzoate , N-4]-chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were compared with rat renal cortical slices. 2 Cisplatin at 1 mM caused toxicity to the slices, as shown b y an increase in the leakage of aspartate aminotransferase and lactate dehydrogenase from the slices into the incubation medium and a decrea se in the reduction of a tetrazolium dye (MTT assay). Addition of proc aine (1 mM) protected against cisplatin-induced toxicity. DPR either a t 1 mM or at 4 mM had no effect either on the enzyme leakage or MTT re duction by the renal slices, but DPR at 10 mM produced a similar magni tude of enzyme leakage to cisplatin (1 mM). 3 DPR loweredthe concentra tion of ATP and glutathione (GSH) in the slices but was less potent th an cisplatin. Thiobarbituric acid reactive substances, indicators of l ipid peroxidation, released into the medium were increased by the high est concentration of DPR (10 mM), which suggests that DPR has the pote ntial to cause oxidative stress. 4 The results suggest that DPR was fa r less toxic than either cisplatin alone or a mixture of cisplatin and procaine.