Nephrotoxicity pp 343-347 | Cite as

Lipid Peroxidation as a Mechanism of Cisplatin-Induced Nephrotoxicity

  • J. Hannemann
  • K. Baumann


Cisplatin (cis-platinum-II-diammine dichloride, CP), an antitumour agent against many solid tumours (1), causes as a major side-effect nephrotoxicity (2). Nephrotoxicity has an occurrence of 25–75% in humans (3), depending on single or multiple course therapy. The mechanism of the CP-induced nephrotoxicity is not well known. The administration of antioxidants or radical scavengers reduces the CP-induced nephrotoxicity in vivo (4–6). Increased in vivo production of the lipid peroxidation product malondialdehyde in the kidney after CP-treatment of the rat, has been shown very recently (5). In the present in vitro study, the effect of CP, and the combined effect of CP and antioxidants or radical scavengers on lipid peroxidation and pyruvate-stimulated gluconeogenesis in rat renal cortical slices were investigated. It has been shown that rat renal cortical slices accumulated CP manifold above the concentration in the incubation medium, involving an interaction with the organic base carrier system at the basolateral side of proximal tubular cells (7). Transport into the tubular cells across the luminal membrane seems not to be a prerequisite of CP-induced nephrotoxicity, since nonfiltering kidneys developed toxicity after CP-treatment (8), and recovery of radiolabelled CP in the urine after microinjection into early segments of proximal tubules was 94% (9).


Toxicity Superoxide Pyruvate Malondialdehyde Toxicology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L.H. Einhorn, Combination chemotherapy with cis-dichlordiammineplatinum (II) in disseminated testicular cancer. Cancer Treat. Rep., 63: 1659 (1979).PubMedGoogle Scholar
  2. 2.
    D.D. Choie, D.S. Longnecker and A.A. del Campo, Acute and chronic cis-platin nephropathy in rats. Lab. Invest., 44:397 (1981).PubMedGoogle Scholar
  3. 3.
    R.S. Goldstein and G.H. Mayor, Minireview: The nephrotoxicity of cisplatin. Life Sci., 32: 685 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    J.E. McGinness, P.H. Proctor, H.B. Demopoulos, J.A. Hokanson and D.S. Kirkpatrick, Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase). Physiol. Chem. Physics, 10: 867 (1978).Google Scholar
  5. 5.
    K. Sugihara, S. Nakano, M. Koda, K. Tanaka, N. Fukuishi and M. Gemba, Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues. Japan. J. Pharmacol., 43:247 (1987).CrossRefGoogle Scholar
  6. 6.
    D.C. Dobyan, J.M. Bull, F.R. Strebel, B.A. Sunderland and R.E. Bulger, Protective effects of O- (ß-hydroxyethyl) -rutoside on cis-platinum induced acute renal failure in the rat. Lab. Invest., 55:557 (1986).PubMedGoogle Scholar
  7. 7.
    R. Safirstein, P. Miller and J.B. Guttenplan, Uptake and metabolism of cisplatin by rat kidney. Kidney Int., 25:753 (1984).PubMedCrossRefGoogle Scholar
  8. 8.
    K. Miura, R.S. Goldstein, D.A. Pasino and J.B. Hook, Cisplatin nephrotoxicity: Role of filtration and tubular transport of cisplatin in isolated perfused kidneys. Toxicology, 44:147 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    R. Safirstein, J. Winston, D. Moel, S. Dikman and J. Guttenplan, Cisplatin nephrotoxicity: Insights into mechanism. Int. J. Androl., 10:325 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    J.A. Buege and S.D. Aust, Microsomal lipid peroxidation. Meth. Enzymol., 52:302 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Roobol and G.A.O. Alleyne, Control of renal cortex ammoniagenesis and its relationship to renal cortex gluconeogenesis. Biochim. Biophys. Acta, 362: 83 (1974).PubMedCrossRefGoogle Scholar
  12. 12.
    C. Cojocel, J. Hannemann and K. Baumann, Cephaloridine-induced lipid peroxidation initiated by reactive oxygen species as a possible mechanism of cephaloridine nephrotoxicity. Biochim. Biophys. Acta, 834:402 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    C. Cojocel, K.H. Laeschke, G. Inselmann and K. Baumann, Inhibition of cephaloridine-induced lipid peroxidation. Toxicology, 35:295 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    R.S. Goldstein, B. Noozdewier, J.T. Bond, J.B. Hook and G.H. Mayor, Cis-dichlorodiammineplatinum nephrotoxicity: Time course and dose response of renal functional impairment. Toxicol. Appl. Pharmacol., 60: 163 (1981).PubMedCrossRefGoogle Scholar
  15. 15.
    C.L. Litterst, M.A. Smith, J.H. Smith, M. Copley and J. Uozumi, Sensitivity of in vitro renal function tests as indicators of cis-platininduced renal toxicity. Third International Symposium on Nephrotoxicity, Guildford, UK, 1987 (Abstract).Google Scholar
  16. 16.
    K. Sugihara, S. Nakano and M. Gemba, Effect of cisplatin on in vitro production of lipid peroxides in rat kidney cortex. Japan. J. Pharmacol., 44:71 (1987).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • J. Hannemann
    • 1
  • K. Baumann
    • 1
  1. 1.Department of Cell Physiology, Institute of PhysiologyUniversity of HamburgHamburg 13Germany

Personalised recommendations