COADMINISTRATION OF THE NEUROTROPHIC ACTH((4-9)) ANALOG, ORG-2766, MAY REDUCE THE COCHLEOTOXIC EFFECTS OF CISPLATIN

In this study the effect of the neurotrophic ACTH((4-9)) analogue, ORG 2766, on cisplatin cochleotoxicity was investigated with both light- and transmission electron microscopy. Guinea pigs were treated with ei ther cisplatin + ORG 2766 (n = 11) or cisplatin + physiological saline (n = 9). All animals treated with cisplatin + physiological saline sh owed complete loss of outer hair cells (OHC) and degeneration of the o rgan of Corti in the basal cochlear turns, while partial OHC loss was found in the middle and apical turns. The inner hair cells (IHC) and o ther cochlear tissues were not affected. Eight animals from the group treated with cisplatin + ORG 2766 demonstrated similar pathological ch anges, but to a lesser degree, especially in the middle turns. The thr ee remaining animals demonstrated no cochlear alterations at all, ligh t-microscopically, and only minor subcellular changes in the OHCs at t he ultrastructural level. Electrophysiologically, these three animals showed normal compound action potential (CAP) amplitudes at stimulus f requencies from 0.5 to 16 kHz and normal cochlear microphonics (CM) in the frequency range from 0.5 to 8 kHz. The other animals treated with cisplatin + ORG 2766 showed a severe loss in their CAPs and CM, excep t for one showing intermediate loss. All animals from the group treate d with cisplatin alone showed a severe loss in their CAPs and CM. Endo lymphatic hydrops was present in all animals from the cisplatin- and t he cisplatin + ORG 2766-treated groups. These data indicate that daily , concomitant administration of ORG 2766 may reduce OHC loss and subse quent degeneration of the organ of Corti in cisplatin-treated guinea p ig cochleas.