, Volume 65, Issue 3, pp 549-556

Effects of cyclooxygenase inhibitor treatment on the renal toxicity of cisplatin in rats

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Abstract

Purpose

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.