Cisplatin-induced neuropathy in mature rats: effects of the melanocortin-derived peptide ORG 2766.
A major side effect of cisplatin treatment is peripheral neuropathy. In the past few years we have provided evidence that the ACTH4-9 analogue ORG 2766 provides protection against this neuropathy in rats and man. In this study we investigated the development of a cisplatin-induced neuropathy and the protective and therapeutic actions of ORG 2766 in mature rats. We also studied the effects of the peptide and of growth impairment caused by food restriction on nerve conduction velocities in healthy young adult rats (not subjected to any other treatment). In the neuropathy experiment, cisplatin induced a significant decrease in sensory nerve conduction velocity (SNCV), which could be prevented by concomitant administration of ORG 2766. The SNCV of the neuropathic animals recovered to control values within 10 weeks of discontinuation of cisplatin treatment. ORG 2766 did not enhance the rate of recovery. In the young adult rats neither ORG 2766 administration nor restricted weight gain significantly influenced either the motor or the sensory nerve conduction velocity. These results validate the animal model of cisplatin-induced neuropathy.
Hamers
F P
FP
Rudolf Magnus Institute, Department of Medical Pharmacology, Utrecht State University, The Netherlands.
Pette
C
C
Bravenboer
B
B
Vecht
C J
CJ
Neijt
J P
JP
Gispen
W H
WH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D004594:Electrophysiology; D005508:Food Deprivation; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D009431:Neural Conduction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin