Medical Oncology

, Volume 20, Issue 2, pp 175–180 | Cite as

Protective effect of amifostine against cisplatin-induced motor neuropathy in rat

  • Suayib Yalcin
  • Gulay Nurlu
  • Bülent Orhan
  • Dilara Zeybek
  • Sevda Müftüoğlu
  • Banu Şarer
  • Berna Akkuş Yildirim
  • Eren Cetin
Original Article


Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination.

The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.

Key Words

Neurotoxicity cisplatin amifostine 


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  1. 1.
    Anand, A.J. and Bashey, B. (1993). New insights into cisplatin nephrotoxicity. Ann. Pharmacother. 27:1519–1525.PubMedGoogle Scholar
  2. 2.
    Orhan, B., et al. (1998). Does cisplatin stimulate erythropoietin secretion from the peritubuler cells of the kidney? Clin. Nephrol. 50:202–203.PubMedGoogle Scholar
  3. 3.
    Aggarwal, S.K. (1993). A histochemical approach to the mechanism of action of cisplatin and its analogs. J. Histochem. Cytochem. 41:1053–1073.PubMedGoogle Scholar
  4. 4.
    Hamers, F.P., et al. (1993). Reduced glutathione protects against cisplatin-induced neurotoxicity in rats. Cancer Res. 53:544–549.PubMedGoogle Scholar
  5. 5.
    Tredici, G., et al. (1994). Low-dose glutathione administration in the prevention of cisplatin-induced peripheral neuropathy in rats. Neurotoxicology 15:701–704.PubMedGoogle Scholar
  6. 6.
    Cavaletti, G., Minoia, C., Schieppati, M. and Tredici, G. (1994). Protective effect of glutathione on cisplatin neurotoxicity in rats. Int. J. Radiat. Oncol. Biol. Phys. 29:771–776.PubMedGoogle Scholar
  7. 7.
    Cece, R., et al. (1995). An ultrastructural study of neuronal changes in dorsal root ganglia (DGR) of rats after chronic cisplatin administrations. Histol. Histopathol. 10:837–845.PubMedGoogle Scholar
  8. 8.
    Tredici, G., et al. (1999). Effect of recombinant nerve growth factor on cisplatin neurotoxicity in rats. Exp. Neurol. 159:551–558.PubMedCrossRefGoogle Scholar
  9. 9.
    DeKoning, P., Neijt, J.P., Jennekens, F.G. and Gispen, W.H. (1987). Evaluation of cis-diamminedichloroplatinum II (cisplatin) neurotoxicity in rats. Toxicol. Appl. Pharmacol. 89:81–87.CrossRefGoogle Scholar
  10. 10.
    Yang, Q., et al. (2000). Effect of maturation on nerve excitability in an experimental model of threshold electrotonus. Muscle Nerve 23:498–506.PubMedCrossRefGoogle Scholar
  11. 11.
    Caveletti, G., et al. (1992). Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats. Acta Neuropathol. (Berl.) 84:364–371.Google Scholar
  12. 12.
    Yalcin, S., et al. (1996). Granulocyte-colony stimulating factor (G-CSF) administration for chemotherapy-induced neutropenia. Hematology 1:155–162.Google Scholar
  13. 13.
    Yalcin, S. and Orhan, B. (1998). Recombinant human erythropoietin in the treatment of chronic anemia of cancer. Acta Haematol. 100:1152.Google Scholar
  14. 14.
    Yalcin, S., Güllü, I., Demiroglu, H. and Tekuzman, G. (1997). Acute leukemia during tamoxifen therapy. Med. Oncol. 14:61–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Yalcin, S., et al. (1999). Serotonin receptor antagonists in prophylaxis of acute and delayed emesis induced by moderately emetogenic single-day chemotherapy: a randomized study. Am. J. Clin. Oncol. 22:94–96.PubMedCrossRefGoogle Scholar
  16. 16.
    Spencer, C.M. and Goa, K.L. (1995). Amifostine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs 50:1001–1031.PubMedGoogle Scholar
  17. 17.
    Santini, V. and Giles, F.J. (1999). The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica 84:1035–1042.PubMedGoogle Scholar
  18. 18.
    Foster-Nora, J.A. and Siden, R. (1997). Amifostine for protection from antineoplastic drug toxicity. Am. J. Health-Syst Pharm. 54:787–800.PubMedGoogle Scholar
  19. 19.
    Tannehill, S.P. and Mehta, M.P. (1996). Amifostine and radiation therapy: past, present, and future. Semin. Oncol. 23(Suppl. 8):69–77.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Suayib Yalcin
    • 1
  • Gulay Nurlu
    • 2
  • Bülent Orhan
    • 6
  • Dilara Zeybek
    • 3
  • Sevda Müftüoğlu
    • 3
  • Banu Şarer
    • 4
  • Berna Akkuş Yildirim
    • 5
  • Eren Cetin
    • 5
  1. 1.Institute of OncologyHacettepe UniversityAnkaraTurkey
  2. 2.Department of NeurologyHacettepe UniversityAnkaraTurkey
  3. 3.Department of Histology and EmbryologyHacettepe UniversityAnkaraTurkey
  4. 4.Department of Internal MedicineHacettepe UniversityAnkaraTurkey
  5. 5.Department of Radiation OncologyHacettepe UniversityAnkaraTurkey
  6. 6.Ali Osman Sönmez Oncology HospitalBursaTurkey

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