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


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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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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