Effects of nifedipine on cisplatinum-induced nephrotoxicity in rats.
The effects of calcium channel blockade with nifedipine (N) on cis-diammine dichloroplatinum II (CDDP)-induced nephrotoxicity were tested in male Sprague-Dawley rats. Renal function was evaluated before and five days after CDDP administration (5 mg/kg). The rats were treated with various doses of N (0.1; 0.3; 0.6 mg/kg/day) 2 days before CDDP administration and throughout the study. The severity of CDDP-induced acute renal failure was markedly modified in N-treated animals according to the daily dosage of N. At 0.3 and 0.6 mg/kg BW/day, N enhanced CDDP nephrotoxicity. Serum creatinine was 637 +/- 45 and 611 +/- 71 mumoles/liter, respectively, 5 days after CDDP administration (vs. 313 +/- 24 mumoles in animals treated with CDDP alone; p less than 0.05). In these animals the plasma potassium level was significantly elevated at day 7 when compared with CDDP-treated and control rats. In contrast, at the dose of 0.1 mg/kg BW/day N attenuated CDDP nephrotoxicity with a serum creatinine of 214 +/- 35 mumoles at the end of the study. The pathologic changes were also more severe in the groups receiving 0.3 and 0.6 mg/kg of nifedipine. We postulate that at the higher doses (0.3 and 0.6 mg/kg) the systemic hemodynamic effects of nifedipine may override the potentially beneficial intrarenal effect which may account for the favorable results recorded with a dosage of 0.1 mg/kg.
Deray
G
G
Department of Nephrology, Hôpital Pitie, Paris, France.
Dubois
M
M
Beaufils
H
H
Cacoub
P
P
Anouar
M
M
Jaudon
M C
MC
Baumelou
A
A
Jouanneau
C
C
Jacobs
C
C
D058186:Acute Kidney Injury / Q000188:drug therapy*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D009543:Nifedipine; D002945:Cisplatin