APPLICATION OF A NEUROPROTECTIVE ACTH(4-9) ANALOG TO AFFECT CISPLATINOTOTOXICITY - AN ELECTROCOCHLEOGRAPHIC STUDY IN GUINEA-PIGS

Ototoxicity and neurotoxicity are among the most serious side-effects of cisplatin therapy. Previous experiments have shown that neurotoxici ty can be delayed or prevented by treatment with the melanocortin-deri ved peptide ORG 2766, and ACTH4-9 analog. A remedy against ototoxicity is not available. In this study we describe cisplatin-induced abnorma lities in cochlear potentials in guinea pigs. These included changes i n compound action potential (CAP), cochlear microphonics (CM) and summ ating potential (SP) at frequencies from 500 Hz to 16 kHz. Cisplatin ( 2 mg/kg for 8 days) reduced CAP amplitude with the effect becoming mor e pronounced at higher frequencies. Cisplatin also reduced CM and SP. Concurrent treatment with ORG 2766 prevented cisplatin ototoxicity par tially or completely in four out of ten animals. In the other six anim als the effects were comparable to those seen in control animals not t reated with the peptide. The protective effects found with this neurot rophic peptide warrant further experimentation.