Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats

The influence of acetylcysteine (ac-cys) on cisplatin (CP) nephrotoxicity was investigated in female Wistar rats. Administration of 0.6 mg CP 100 g-1 body wt. was followed by oliguria and proteinuria, as well as a significant increase of blood urea nitrogen concentration. The i.p. administration of 0.6 mg CP 100 g-1 body wt. concomitantly with 100 mg ac-cys 100 g-1 body wt. s.c. completely abolished the nephrotoxic effects of CP. However, following this, the Pt concentration in kidney was decreased significantly by ac-cys treatment. This was caused by the enhanced urinary excretion of Pt. The same effect on CP nephrotoxicity appeared when CP and ac-cys were dissolved together in solution prior to injection. It could be shown that in this solution a ligand exchange reaction of CP by ac-cys started immediately, resulting in increased renal excretion and decreased Pt concentration in kidney. From our results we concluded that the protective effect of ac-cys on CP nephrotoxicity is based on the formation of a complex unsuitable for tubular reabsorption.