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. 1989 Jun;97(2):313–318. doi: 10.1111/j.1476-5381.1989.tb11956.x

Effect of aminophylline on cisplatin nephrotoxicity in the rat.

H T Heidemann 1, S Müller 1, L Mertins 1, G Stepan 1, K Hoffmann 1, E E Ohnhaus 1
PMCID: PMC1854525  PMID: 2758217

Abstract

1. The effect of the methylxanthine aminophylline on cisplatin (5 mg kg-1 i.v.)-induced acute renal failure was investigated in the rat. Renal function was measured 5 days after cisplatin administration. 2. Cisplatin caused a polyuric acute renal failure. The creatinine clearance was significantly reduced. 3. Aminophylline (24 mg kg-1 12h-1) ameliorated the cisplatin nephrotoxicity when administered during the maintenance phase of acute tubular necrosis. However, it had no effect when only administered prophylactically before the cisplatin application. 4. Enprofylline (20 mg kg-1 4h-1 with dose adjustment), a methylxanthine lacking adenosine receptor antagonism in comparison to aminophylline, had no protective effect on cisplatin nephrotoxicity. 5. Adenosine is a renal vasoconstrictor and decreases glomerular filtration rate. Endogenous adenosine in the kidney is formed by degradation of ATP and is thought to be involved in various forms of acute renal failure. The results suggest that adenosine may be involved in the haemodynamic changes in the kidney induced by cisplatin.

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Selected References

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  1. Bidani A. K., Churchill P. C. Aminophylline ameliorates glycerol-induced acute renal failure in rats. Can J Physiol Pharmacol. 1983 Jun;61(6):567–571. doi: 10.1139/y83-087. [DOI] [PubMed] [Google Scholar]
  2. Bowmer C. J., Collis M. G., Yates M. S. Effect of the adenosine antagonist 8-phenyltheophylline on glycerol-induced acute renal failure in the rat. Br J Pharmacol. 1986 May;88(1):205–212. doi: 10.1111/j.1476-5381.1986.tb09488.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chopra S., Kaufman J. S., Jones T. W., Hong W. K., Gehr M. K., Hamburger R. J., Flamenbaum W., Trump B. F. Cis-diamminedichlorplatinum-induced acute renal failure in the rat. Kidney Int. 1982 Jan;21(1):54–64. doi: 10.1038/ki.1982.8. [DOI] [PubMed] [Google Scholar]
  4. Churchill P. C., Bidani A. K. Hypothesis: adenosine mediates hemodynamic changes in renal failure. Med Hypotheses. 1982 Mar;8(3):275–285. doi: 10.1016/0306-9877(82)90124-4. [DOI] [PubMed] [Google Scholar]
  5. Gerkens J. F., Heidemann H. T., Jackson E. K., Branch R. A. Effect of aminophylline on amphotericin B nephrotoxicity in the dog. J Pharmacol Exp Ther. 1983 Mar;224(3):609–613. [PubMed] [Google Scholar]
  6. Goldstein R. S., Mayor G. H. Minireview. The nephrotoxicity of cisplatin. Life Sci. 1983 Feb 14;32(7):685–690. doi: 10.1016/0024-3205(83)90299-0. [DOI] [PubMed] [Google Scholar]
  7. Heidemann H. T., Gerkens J. F., Jackson E. K., Branch R. A. Attenuation of cisplatinum-induced nephrotoxicity in the rat by high salt diet, furosemide and acetazolamide. Naunyn Schmiedebergs Arch Pharmacol. 1985 Apr;329(2):201–205. doi: 10.1007/BF00501213. [DOI] [PubMed] [Google Scholar]
  8. Heidemann H. T., Gerkens J. F., Jackson E. K., Branch R. A. Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(2):148–152. doi: 10.1007/BF00497021. [DOI] [PubMed] [Google Scholar]
  9. Lin J. J., Churchill P. C., Bidani A. K. The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats. Can J Physiol Pharmacol. 1987 Jul;65(7):1491–1495. doi: 10.1139/y87-233. [DOI] [PubMed] [Google Scholar]
  10. Lin J. J., Churchill P. C., Bidani A. K. Theophylline in rats during maintenance phase of post-ischemic acute renal failure. Kidney Int. 1988 Jan;33(1):24–28. doi: 10.1038/ki.1988.4. [DOI] [PubMed] [Google Scholar]
  11. Loehrer P. J., Einhorn L. H. Drugs five years later. Cisplatin. Ann Intern Med. 1984 May;100(5):704–713. doi: 10.7326/0003-4819-100-5-704. [DOI] [PubMed] [Google Scholar]
  12. Lunell E., Svedmyr N., Andersson K. E., Persson C. G. A novel bronchodilator xanthine apparently without adenosine receptor antagonism and tremorogenic effect. Eur J Respir Dis. 1983 Jul;64(5):333–339. [PubMed] [Google Scholar]
  13. Lunell E., Svedmyr N., Andersson K. E., Persson C. G. Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease. Eur J Clin Pharmacol. 1982;22(5):395–402. doi: 10.1007/BF00542541. [DOI] [PubMed] [Google Scholar]
  14. Miller W. L., Thomas R. A., Berne R. M., Rubio R. Adenosine production in the ischemic kidney. Circ Res. 1978 Sep;43(3):390–397. doi: 10.1161/01.res.43.3.390. [DOI] [PubMed] [Google Scholar]
  15. Osswald H., Nabakowski G., Hermes H. Adenosine as a possible mediator of metabolic control of glomerular filtration rate. Int J Biochem. 1980;12(1-2):263–267. doi: 10.1016/0020-711x(80)90082-8. [DOI] [PubMed] [Google Scholar]
  16. Osswald H. Renal effects of adenosine and their inhibition by theophylline in dogs. Naunyn Schmiedebergs Arch Pharmacol. 1975;288(1):79–86. doi: 10.1007/BF00501815. [DOI] [PubMed] [Google Scholar]
  17. Osswald H., Schmitz H. J., Kemper R. Tissue content of adenosine, inosine and hypoxanthine in the rat kidney after ischemia and postischemic recirculation. Pflugers Arch. 1977 Oct 19;371(1-2):45–49. doi: 10.1007/BF00580771. [DOI] [PubMed] [Google Scholar]
  18. Osswald H., Spielman W. S., Knox F. G. Mechanism of adenosine-mediated decreases in glomerular filtration rate in dogs. Circ Res. 1978 Sep;43(3):465–469. doi: 10.1161/01.res.43.3.465. [DOI] [PubMed] [Google Scholar]
  19. Persson C. G., Karlsson J. A., Erjefält I. Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives. Life Sci. 1982 Jun 21;30(25):2181–2189. doi: 10.1016/0024-3205(82)90292-2. [DOI] [PubMed] [Google Scholar]
  20. Safirstein R., Miller P., Dikman S., Lyman N., Shapiro C. Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity. Am J Physiol. 1981 Aug;241(2):F175–F185. doi: 10.1152/ajprenal.1981.241.2.F175. [DOI] [PubMed] [Google Scholar]
  21. THURAU K. RENAL HEMODYNAMICS. Am J Med. 1964 May;36:698–719. doi: 10.1016/0002-9343(64)90181-0. [DOI] [PubMed] [Google Scholar]
  22. Ward J. M., Grabin M. E., LeRoy A. F., Young D. M. Modification of the renal toxicity of cis-dichlorodiammineplatinum(II) with furosemide in male F344 rats. Cancer Treat Rep. 1977 May-Jun;61(3):375–379. [PubMed] [Google Scholar]
  23. Winston J. A., Safirstein R. Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat. Am J Physiol. 1985 Oct;249(4 Pt 2):F490–F496. doi: 10.1152/ajprenal.1985.249.4.F490. [DOI] [PubMed] [Google Scholar]

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