PROTECTION AGAINST CISPLATIN-INDUCED NEUROTOXICITY BY ORG-2766 - HISTOLOGICAL AND ELECTROPHYSIOLOGICAL EVIDENCE

Prolonged administration of the anti-tumor agent cisplatin may cause a neuropathy in patients. In an animal model, too, neurotoxicity, as ev idenced by a decrease in H-related sensory nerve conduction velocity ( SNCV), can be induced by repetitive injections of cisplatin. In an att empt to further the insight into the effects of cisplatin on the perip heral nervous system a combined electrophysiological and histomorpholo gical investigation was performed on 2 groups of 6 rats, treated with cisplatin for 7.5 weeks, and a control group (n = 6). Concomitant admi nistration of ORG 2766, an ACTH(4-9) analog, was previously shown to p revent cisplatin neurotoxicity in this model and more recently in pati ents as well. One group of rats was therefore co-treated with this pep tide during the complete treatment period. A marked decrease in SCNV w as observed in cisplatin/saline treated rats, but not in cisplatin/ORG 2766 treated rats. Though no statistically significant difference was seen in the total number of myelinated fibers in the sural nerves of cisplatin treated rats, a decrease in the proportion of thick myelinat ed fibers was present in the cisplatin/saline treated rats. This shift in fiber distribution was absent in ORG 2766 co-treated animals. Mean internodal distances and g-ratios were not affected, and signs of axo nal degeneration, or de- or remyelination were not observed.