Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats.
The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
Martinez
F
F
Department of Nephrology, Hôpital Pitie, Paris, France.
Deray
G
G
Dubois
M
M
Beaufils
H
H
Jacquiaud
C
C
Bourbouze
R
R
Benhmida
M
M
Jaudon
M C
MC
Jacobs
C
C
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016190:Carboplatin / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003681:Dehydration / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004361:Drug Tolerance; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014882:Water-Electrolyte Balance / Q000187:drug effects
D003404:Creatinine; D016190:Carboplatin; D002945:Cisplatin