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.
Appenroth
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany.
Winnefeld
K
K
Schröter
H
H
Rost
M
M
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006207:Half-Life; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D010984:Platinum / Q000097:blood / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D014563:Urodynamics / Q000187:drug effects
D010984:Platinum; D002945:Cisplatin; D000111:Acetylcysteine