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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.

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References

  1. Bellmunt J, Albiol S (2007) Chemotherapy for metastatic or unresectable bladder cancer. Semin Oncol 34:135–144

    Article  CAS  PubMed  Google Scholar 

  2. Sternberg CN, Donat SM, Bellmunt J et al (2007) Chemotherapy for bladder cancer: Treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology 696:62–79

    Article  Google Scholar 

  3. Knapp DW, Glickman NW, Widmer WR et al (2000) Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 46:221–226

    Article  CAS  PubMed  Google Scholar 

  4. Knapp DW (2006) Animal models: naturally occurring canine urinary bladder cancer. In: Lerner SP, Schoenberg MP, Sternberg CN (eds) Textbook of bladder cancer. Taylor & Francis, Oxon, pp 171–175

    Google Scholar 

  5. Daugaard G (1990) Cisplatin nephrotoxicity: experimental and clinical studies. Dan Med Bull 37:1–12

    CAS  PubMed  Google Scholar 

  6. Anand AJ, Bashey B (1993) Newer insights into cisplatin nephrotoxicity. Ann Pharmacother 27:1519–1525

    CAS  PubMed  Google Scholar 

  7. Tsuruya K, Ninomiya T, Tokumoto M et al (2003) Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Kidney Int 63:72–82

    Article  CAS  PubMed  Google Scholar 

  8. Sheikh-Hamad D, Cacini W, Buckley AR et al (2004) Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney. Arch Toxicol 78:147–155

    Article  CAS  PubMed  Google Scholar 

  9. Khan KN, Venturini CM, Bunch RT et al (1998) Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity. Toxicol Pathol 26:612–620

    Article  CAS  PubMed  Google Scholar 

  10. Whelton A (1999) Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 106:13S–24S

    Article  CAS  PubMed  Google Scholar 

  11. Bosch-Marce M, Claria J, Titos E et al (1999) Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology 116:1167–1175

    Article  CAS  PubMed  Google Scholar 

  12. Khan KN, Paulson SK, Verburg KM et al (2002) Pharmacology of cyclooxygenase-2 inhibition in the kidney. Kidney Int 61:1210–1219

    Article  CAS  PubMed  Google Scholar 

  13. Hocherl K, Kammerl MC, Schmuacher K et al (2002) Role of prostanoids in regulation of the rennin–angiotensin–aldosterone system by salt intake. Am J Physio Renal Physiol 283:F294–F301

    CAS  Google Scholar 

  14. Lopez-Parra M, Claria J, Planaguma A, Titos E et al (2002) Cyclooxygenase-1 derived prostaglandins are envolved in the maintenance of renal function in rats with cirrhosis and ascites. Brit J Pharmacol 135:891–900

    Article  CAS  Google Scholar 

  15. Mohammed SI, Knapp DW, Bostwick DG et al (1999) Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 59:5647–5650

    CAS  PubMed  Google Scholar 

  16. Khan KN, Knapp DW, Denicola DB, Harris RK (2000) Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs. Am J Vet Res 61:478–481

    Article  CAS  PubMed  Google Scholar 

  17. Mizutani Y, Nakanishi H, Li YN et al (2004) Enhanced sensitivity of bladder cancer cells to cisplatin mediated cytotoxicity and apoptosis in vitro and in vivo by the selective cyclooxygenase-2 inhibitor JTE-522. J Urol 172:1474–1479

    Article  CAS  PubMed  Google Scholar 

  18. Dobyan DC, Levi J, Jacobs C et al (1980) Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther 213:551–556

    CAS  PubMed  Google Scholar 

  19. Ries F, Klastersky J (1986) Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am J Kidney Dis 8:368–379

    CAS  PubMed  Google Scholar 

  20. Zhou H, Kato A, Yasuda H, Odamaki M, Itoh H, Hishida A (2003) The induction of heat shock protein-72 attenuates cisplatin-induced acute renal failure in rats. Pflugers Archiv Eur J Physiol 446:116–124

    CAS  Google Scholar 

  21. Masferrer JL, Koki A, Seibert K (1999) Cox-2 inhibitors. A new class of antiangiogenic agents. Ann NY Acad Sci 889:84–86

    Article  CAS  PubMed  Google Scholar 

  22. Tegeder I, Neiderberger E, Vetter G et al (2001) Effects of selective cox-1 and -2 inhibition on formalin-evoked nociceptive behaviour and prostaglandin E2 release in the spinal cord. J Neurochem 79:777–786

    Article  CAS  PubMed  Google Scholar 

  23. Zhang Y-H, Lu J, Elmquist JK, Saper CB (2003) Specific roles of cyclooxygenase-1 and cyclooxygenase-2 in lipopolysaccharide-induced fever and fos expression in rat brain. J Comp Neurol 463:3–12

    Article  CAS  PubMed  Google Scholar 

  24. Chopra S, Kaufman JS, Jones TW et al (1982) Cis-diamminedichlorplatinum-induced acute renal failure in the rat. Kidney Int 21:54–64

    Article  CAS  PubMed  Google Scholar 

  25. Ecelbarger CA, Sands JM, Doran JJ et al (2001) Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria. Kidney Int 60:2274–2282

    Article  CAS  PubMed  Google Scholar 

  26. Osman NM, Copley MP, Litterst CL (1984) Effects of the diuretics mannitol or acetazolamide on nephrotoxicity and physiological disposition of cisplatin in rats. Cancer Chemother Pharmacol 13:58–62

    Article  CAS  PubMed  Google Scholar 

  27. Huang Q, Dunn RTII, Jayadev S, DiSorbo O et al (2001) Assessment of cisplatin-induced nephrotoxicity by microarray technology. Toxicol Sci 63:196–207

    Article  CAS  PubMed  Google Scholar 

  28. Rooseboom M, Schaaf G, Commandeur JN et al (2002) Beta-lyase-dependent attenuation of cisplatin-mediated toxicity by selenocysteine Se-conjugates in renal tubular cell lines. J Pharmacol Exp Ther 301:884–892

    Article  CAS  PubMed  Google Scholar 

  29. Harris RC (2006) COX-2 and the kidney. J Cardiovas Pharmacol 47:S37–S42

    Article  CAS  Google Scholar 

  30. Launay-Vacher V, Rey JB, Isnard-Bagnis C et al (2008) European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol 61:903–909

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported in part by an American Kennel Club ACORN grant.

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Authors and Affiliations

  1. 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

    Shawna N. Greene, Cheryl Anderson, Lindsey M. Fourez, Brenda M. Johnson, Jane C. Stewart & Deborah W. Knapp

  2. Department of Comparative Pathobiology, Purdue University School of Veterinary Medicine, West Lafayette, IN, 47907, USA

    José A. Ramos-Vara & Steven B. Hooser

  3. Department of Statistics, Purdue University, West Lafayette, IN, 47907, USA

    Bruce A. Craig

  4. Purdue Cancer Center and Oncological Sciences Center, Purdue University, West Lafayette, IN, 47907, USA

    Deborah W. Knapp

Authors
  1. Shawna N. Greene
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  2. José A. Ramos-Vara
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  3. Bruce A. Craig
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  4. Steven B. Hooser
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  5. Cheryl Anderson
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  6. Lindsey M. Fourez
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  7. Brenda M. Johnson
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  8. Jane C. Stewart
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  9. Deborah W. Knapp
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Correspondence to Deborah W. Knapp.

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Greene, S.N., Ramos-Vara, J.A., Craig, B.A. et al. Effects of cyclooxygenase inhibitor treatment on the renal toxicity of cisplatin in rats. Cancer Chemother Pharmacol 65, 549–556 (2010). https://doi.org/10.1007/s00280-009-1061-2

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  • DOI: https://doi.org/10.1007/s00280-009-1061-2

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