Effects of cyclooxygenase inhibitor treatment on the renal toxicity of cisplatin in rats.
OBJECTIVE
The purpose of this study was to determine the effects of a nonselective cyclooxygenase (cox) inhibitor and of a selective cox-2 inhibitor on the renal toxicity of cisplatin.


METHODS
Cisplatin with or without a cox-1 inhibitor (SC560), a cox-2 inhibitor (SC236), or a nonselective cox inhibitor (piroxicam) was administered to Sprague-Dawley rats. Renal toxicity was assessed by serum creatinine concentration (SCR), urine specific gravity (USG), and histopathologic lesion score (HLS).


RESULTS
Acutely, the SCR was significantly higher in rats receiving cisplatin/SC560 (1.62+/-0.34 mg/dl) or cisplatin/piroxicam (2.0+/-0.41 mg/dl) than in rats receiving cisplatin alone (1.09+/-0.40 mg/dl). The apparent increase in SCR in the rats receiving cisplatin/SC236 (1.58+/-0.31) was not significantly different from that of rats receiving cisplatin alone (1.09+/-0.40 mg/dl). No significant differences in USG or HLSs were noted between rats receiving cisplatin alone and cisplatin combined with any cox inhibitor. In a chronic study, no differences in renal toxicity were found between rats treated with cisplatin alone and cisplatin/SC236 or cisplatin/piroxicam.


CONCLUSIONS
The acute rise in SCR following cisplatin treatment can be worsened by the addition of cox inhibitors, especially those that inhibit cox-1.
Greene
Shawna N
SN
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Lynn Hall of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, IN 47907-2026, USA.
Ramos-Vara
José A
JA
Craig
Bruce A
BA
Hooser
Steven B
SB
Anderson
Cheryl
C
Fourez
Lindsey M
LM
Johnson
Brenda M
BM
Stewart
Jane C
JC
Knapp
Deborah W
DW
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D008297:Male; D010865:Pilot Projects; D010894:Piroxicam / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D003404:Creatinine; D002945:Cisplatin