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European Archives of Oto-Rhino-Laryngology

, Volume 251, Issue 1, pp 23–29 | Cite as

Application of a neuroprotective ACTH(4–9) analog to affect cisplatin ototoxicity: an electrocochleographic study in guinea pigs

  • F. P. T. Hamers
  • S. F. L. Klis
  • W. H. Gispen
  • G. F. Smoorenburg
Original paper

Abstract

Ototoxicity and neurotoxicity are among the most serious side-effects of cisplatin therapy. Previous experiments have shown that neurotoxicity can be delayed or prevented by treatment with the melanocortin-derived peptide ORG 2766, and ACTH4–9 analog. A remedy against ototoxicity is not available. In this study we describe cisplatin-induced abnormalities in cochlear potentials in guinea pigs. These included changes in compound action potential (CAP), cochlear microphonics (CM) and summating potential (SP) at frequencies from 500 Hz to 16 kHz. Cisplatin (2 mg/kg for 8 days) reduced CAP amplitude with the effect becoming more pronounced at higher frequencies. Cisplatin also reduced CM and SP. Concurrent treatment with ORG 2766 prevented cisplatin ototoxicity partially or completely in four out of ten animals. In the other six animals the effects were comparable to those seen in control animals not treated with the peptide. The protective effects found with this neurotrophic peptide warrant further experimentation.

Key words

Cisplatin chemotherapy Ototoxicity Prophylaxis Cochlear potentials Guinea pig 

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References

  1. 1.
    Anniko M, Sobin A (1986) Cisplatin: evaluation of its ototoxic potential. Am J Otolaryngol 7:276–293Google Scholar
  2. 2.
    Bar PRD, Schrama LH, Gispen WH (1990) Neurotrophic effects of the ACTH/MSH-like peptides in the peripheral nervous system. In: De Wied D (ed) Neuropeptide concept. Elsevier, Amsterdam, pp 175–211Google Scholar
  3. 3.
    Barr-Hamilton RM, Metheson LM, Keay DG (1991) Ototoxicity of cisplatin and its relationship to eye colour. J Laryngol Otol 105:7–11Google Scholar
  4. 4.
    Barron SE, Daigneault EA (1987) Effect of cisplatin on hair cell morphology and lateral wall Na, K-ATPase activity. Hear Res 26:131–137Google Scholar
  5. 5.
    Bodenner DL, Dedon PC, Keng PC, Katz JC, Borch RF (1986) Selective protection against cis-diamminedichloro-platinum(II) induced toxicity in kidney, gut, and bone marrow by diethyldithiocarbamate. Cancer Res 46:2751–2755Google Scholar
  6. 6.
    Carenza L, Villani C, Framarino dei Malatesta ML, Prosperi Porta R, Millefiorine M, Antonini G, Bolasco P, Bandiera G, Marzetti L (1986) Peripheral neuropathy and ototoxicity of dichlorodiamineplatinum: instrumental evaluation. Gynecol Oncol 25:244–249Google Scholar
  7. 7.
    Charry KK, Highby DJ, Henderson ES, Swenerton KD (1977) Phase-I study of high dose cis-dichlorodiammine-platinum(II) with forced diuresis. Cancer Treat Rep 61:367–370Google Scholar
  8. 8.
    De Koning P, Neijt JP, Jennekens FGI, Gispen WH (1988) ORG 2766 protects from cisplatin-induced neurotoxicity in rats. Exp Neurol 97:746–750Google Scholar
  9. 9.
    Di Re F, Bohm S, Oriana S, Spatti GB, Zunino F (1990) Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer. Cancer Chemother Pharmacol 25: 355–360Google Scholar
  10. 10.
    Dreschler WA, Van der Hulst RJAM, Tange RA, Urbanus NAM (1989) Role of high-frequency audiometry in the early detection of ototoxicity. Audiology 28:211–220Google Scholar
  11. 11.
    Gerritsen van der Hoop R, Brakkee JH, Kapelle A, Samson M, De Koning P, Gispen WH (1988) A new technique to evaluate recovery after peripheral nerve damage: neurotrophic activity of Org 2766. J Neurosci Methods 26:111–116Google Scholar
  12. 12.
    Gerritsen van der Hoop R, Vecht CJ, Van der Burg MEL, Elderson A, Boogerd W, Heimans JJ, Els D, Vries P, Van Houwelingen JC, Jennekens FGI, Gispen WH, Neijt JP (1990) Prevention of cisplatin neurotoxicity with an ACTH(4–9) analogue in patients with ovarian cancer. N Engl J Med 322: 89–94PubMedGoogle Scholar
  13. 13.
    Glover D, Grabelsky S, Fox K, Weiler C, Cannon L, Glick JH (1989) Clinical trials of WR-2721 and cis-platinum. Int J Radiat Oncol Biol Phys 16:1201–1204Google Scholar
  14. 14.
    Gratton MA, Salvi RJ, Kamen BA, Saunders SS (1990) Interaction of cisplatin and noise on the peripheral auditory system. Hear Res 50:211–224Google Scholar
  15. 15.
    Hamers FPT, Gerritsen van der Hoop R, Steerenburg PA, Neijt JP, Gispen WH (1991) Putative neurotrophic factors in the protection of cisplatin-induced peripheral neuropathy in rats. Toxicol Appl Pharmacol 111: 514–522Google Scholar
  16. 16.
    Hasko JA, Richardson GP, Russell IJ, Shaw G (1990) Transient expression of neurofilament protein during hair cell development in the mouse cochlea. Hear Res 45:63–74Google Scholar
  17. 17.
    Kohn S, Fradis M, Pratt H, Zidan J, Podosin L, Robinson E, Nir I (1988) Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis. Laryngoscope 98:865–871Google Scholar
  18. 18.
    Konishi T, Gupta BN, Prazma J (1983) Ototoxicity of cisdichlorodiammine platinum (II) in guinea pigs. Am J Otolaryngol 4:18–26Google Scholar
  19. 19.
    Laurell G, Bagger-Sjöbäck D (1991) Degeneration of the organ of Corti following intravenous administration of cisplatin. Acta Otolaryngol (Stockh) 111:891–898Google Scholar
  20. 20.
    Laurell G, Engström B (1989) The ototoxic effect of cisplatin on guinea pig in relation to dosage. Hear Res 38:27–34Google Scholar
  21. 21.
    Laurell G, Skedinger M (1990) Changes of stapedius reflex and hearing threshold in patients receiving high-dose cisplatin treatment. Audiology 29:252–261Google Scholar
  22. 22.
    Lefebvre PP, Weber T, Rigo JM, Staecker H, Moonen G, Van de Water T (1992) Peripheral and central target-derived trophic factor(s) effects on auditory neurons. Hear Res 58:185–192Google Scholar
  23. 23.
    McAlpine D, Johnstone BM (1990) The ototoxic mechanism of cisplatin. Hear Res 47:191–204Google Scholar
  24. 24.
    Nakai Y, Konishi K, Chang KC, Ohashi K, Morisaki N, Minowa Y, Morimoto A (1982) Ototoxicity of the anticancer drug cisplatin. Acta Otolaryngol (Stockh) 93:227–232Google Scholar
  25. 25.
    Otto WC, Brown RD, Gage-White L, Kupetz S, Anniko M, Penny JE, Henley CM (1988) Effects of cisplatin and thiosulphate upon auditory brainstem responses of guinea pigs. Hear Res 35:79–86Google Scholar
  26. 26.
    Pfeifle GE, Howell SB, Felthouse RD (1985) High-dose cisplatin with sodium thiosulphate protection. J Clin Oncol 3: 237–244Google Scholar
  27. 27.
    Schaeffer SD, Post JD, Close LG, Wright CG (1985) Ototoxicity of low- and moderate-dose cisplatin. Cancer 56:1934–1939Google Scholar
  28. 28.
    Strand FL, Rose KJ, Zuccarelli LA, Kume J, Alves SE, Antonawich FJ, Garrett LY (1991) Neuropeptide hormones as neurotrophic factors. Physiol Rev 71:1017–1046Google Scholar
  29. 29.
    Van Deelen GW, Smoorenburg GF (1986) Electrocochleography for different electrode positions in guinea pigs. Acta Otolaryngol (Stockh) 101:207–216Google Scholar
  30. 30.
    Waters GS, Ahmad M, Katsarkas A, Stanimir G, McKay J (1991) Ototoxicity due to cis-diamminedichloroplatinum in the treatment of ovarian cancer: influence of dosage and schedule of administration. Ear Hear 12:91–102Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • F. P. T. Hamers
    • 1
  • S. F. L. Klis
    • 2
  • W. H. Gispen
    • 1
  • G. F. Smoorenburg
    • 2
  1. 1.Rudolf Magnus Institute, Department of Medical PharmacologyUtrecht UniversityUtrechtThe Netherlands
  2. 2.Laboratory of Experimental Audiology, Department of OtorhinolaryngologyUtrecht UniversityUtrechtThe Netherlands

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