The influence of acetylcysteine (ac-cys) on cisplatin (CP) nephrotoxic
ity was investigated in female Wistar rats. Administration of 0.6 mg C
P 100 g-1 body wt. was followed by oliguria and proteinuria, as well a
s 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-cvs 100 g-1 body wt. s.c. completely abolished the nephrotoxic e
ffects of CP. However, following this, the Pt concentration in kidney
was decreased significantly by ac-cys treatment. This was caused by th
e enhanced urinary excretion of Pt. The same effect on CP nephrotoxici
ty appeared when CP and ac-cys were dissolved together in solution pri
or to injection. It could be shown that in this solution a ligand exch
ange reaction of CP by ac-cys started immediately, resulting in increa
sed renal excretion and decreased Pt concentration in kidney. From our
results we concluded that the protective effect of ac-cys on CP nephr
otoxicity is based on the formation of a complex unsuitable for tubula
r reabsorption.