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Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats
Author(s) -
Appenroth Dorothea,
Winnefeld Klaus,
Schröter Heinz,
Rost Michael
Publication year - 1993
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550130309
Subject(s) - acetylcysteine , nephrotoxicity , cisplatin , pharmacology , toxicity , medicine , toxicology , chemistry , chemotherapy , antioxidant , biology , biochemistry
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.