Application of a neuroprotective ACTH(4-9) analog to affect cisplatin ototoxicity: an electrocochleographic study in guinea pigs.
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.
Hamers
F P
FP
Rudolf Magnus Institute, Department of Medical Pharmacology, Utrecht University, The Netherlands.
Klis
S F
SF
Gispen
W H
WH
Smoorenburg
G F
GF
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001300:Audiometry, Evoked Response; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D009410:Nerve Degeneration / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010919:Placebos; D000159:Vestibulocochlear Nerve / Q000187:drug effects
D010446:Peptide Fragments; D010919:Placebos; C013765:Org 2766; C028024:ACTH (4-9); D000324:Adrenocorticotropic Hormone; D002945:Cisplatin