CISPLATIN-INDUCED CHANGES IN ADENINE-NUCLEOTIDES IN RAT-KIDNEY SLICES- AMELIORATION BY TIOPRONIN AND PROCAINE

The adenine nucleotides (ATP, ADP and AMP) in rat renal cortical slice s exposed in-vitro to cisplatin, an anticancer drug, were determined b y HPLC. Cisplatin had no effect on total adenine nucleotides in the sl ices but caused a time-and concentration-dependent decrease in ATP lev els with a concomitant increase in ADP and AMP levels. The decrease in ATP and increases in ADP and AMP concentrations became statistically significant after incubation with cisplatin (2 mM) for 90 min or after cisplatin (1 mM) for 120 min. Both tiopronin, a sulphydryl-containing drug, and procaine, an antioxidant, protected against cisplatin-induc ed changes in the adenine nucleotides. The results indicate a cisplati n-induced defect in cellular energetics that occurs at a relatively la te stage in the process of toxicity to the slices in this in-vitro mod el. Cisplatin-induced depletion of ATP in the slices might result from an increase in catabolism of ATP to ADP and AMP. Maintenance of the n ormal concentration of ATP in the slices might be involved in the prot ection afforded by tiopronin and procaine against cisplatin-induced ne phrotoxicity.