Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats.
In rats chronic systemic treatment with cisplatin results in a sensory neuropathy as evidenced by a reduction in the sensory conduction velocity in the sciatic nerve. Concomitant administration of the neurotrophic ACTH4-9 analog, ORG.2766, prevents the occurrence of the neuropathy. In addition, treatment with ORG.2766 stops further deterioration and improves recovery of an already established cisplatin-induced neuropathy. Furthermore, concomitant administration of ORG.2766 during a first cisplatin treatment period results in a better resistance against neurotoxicity in a second exposure period. Finally, ORG.2766 was shown not to hamper the anti-tumor effect of cisplatin in mice, carrying implanted tumor cells from a FMa human tumor line. These data are discussed in view of the potential clinical use of ORG.2766 in prevention and treatment of cisplatin-induced neuropathy.
Gerritsen van der Hoop
R
R
Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
de Koning
P
P
Boven
E
E
Neijt
J P
JP
Jennekens
F G
FG
Gispen
W H
WH
D000230:Adenocarcinoma / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin