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 slices exposed in-vitro to cisplatin, an anticancer drug, were determined by HPLC. Cisplatin had no effect on total adenine nucleotides in the slices but caused a time- and concentration-dependent decrease in ATP levels 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-induced changes in the adenine nucleotides. The results indicate a cisplatin-induced defect in cellular energetics that occurs at a relatively late stage in the process of toxicity to the slices in this in-vitro model. Cisplatin-induced depletion of ATP in the slices might result from an increase in catabolism of ATP to ADP and AMP. Maintenance of the normal concentration of ATP in the slices might be involved in the protection afforded by tiopronin and procaine against cisplatin-induced nephrotoxicity.
Zhang
J G
JG
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Lindup
W E
WE
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004338:Drug Combinations; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D011343:Procaine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D008625:Tiopronin / Q000494:pharmacology*
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D000975:Antioxidants; D004338:Drug Combinations; D011343:Procaine; D008625:Tiopronin; D002945:Cisplatin