Nephrotoxic effects of platinum cytostatics--preventative effects of nifedipine and cimetidine.
The study focuses on the observation of nephrotoxic effects of cis-platinum (cis-dichloro-diaminoplatinum, CDDP) and carboplatinum (cis-diamino-cyclobutancarboxyplatinum, CBDCP) and these to affect them by applying Ca-channel blocker (nifedipine) and a selective antagonist of tubular secretion of organic cations (cimetidine). The urine levels of tubular enzymes alkaline phospatase (AP), gamma-glutamyl-transferase (GMT) and N-acetyl-beta-D-glucosaminidase were selected for the evaluation or tubular toxicity. The clearance of endogenous creatinine was observed as well. The experiments were carried out on male rats of outbred Wistar strain within 7 days after the cytostatics had been applied. A significant increase of urine levels of all enzymes studied was observed in animals, which were given CBDCP only. A maximum change was observed in the urine excretion of NAG. Nifedipine application decreased the change significantly, cimetidine had no effect. The effect of combined nifedipine and cimetidine application did not vary from the effect of application of nifedipine itself. In animals given CDDP only, a significant increase of urine levels of all studied enzymes was proved, the maximum change was observed in NAG excretion. This change significantly decreased by nifedipine application. The same effect was reached by cimetidine application. Preventive effects of nifedipine and cimetidine potentiated mutually each other. In conclusion we consider nifedipine as a convenient prevention of CDDP and CBDCP nephrotoxic effects while cimetidine can be used as a prevention of CDDP nephrotoxic effect only.
Haragsim
L
L
1st Department of Medical Chemistry and Biochemistry, 1st Medical Faculty, Charles University, Prague, Czech Republic.
Zima
T
T
Nĕmecek
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016190:Carboplatin / Q000633:toxicity*; D002927:Cimetidine / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D002927:Cimetidine; D016190:Carboplatin; D009543:Nifedipine; D002945:Cisplatin