Valproate protective effects on cisplatin-induced peripheral neuropathy: an in vitro and in vivo study.
BACKGROUND
Antineoplastic drugs, such as cisplatin (CDDP), induce disabling peripheral neuropathies, representing a hindrance to effective cancer treatments. The exact pathogenesis of CDDP-induced neuropathy is not yet understood, and the dysregulation of gene expression has been proposed. Valproate (VPA) is an antiepileptic drug recently discovered to remodel gene expression, with hypothetically putative neuroprotective effects.


METHODS
VPA was tested in both, in vitro and in vivo models of CDDP-neurotoxicity.


RESULTS
VPA administered in combination with CDDP promoted dorsal root ganglia (DRG) neurons survival. Moreover, this treatment induced in Wistar rats an improvement of body weight, sensory nerve conduction velocity, and DRG morphometric analysis. In contrast, VPA was not able to rescue CDDP pre-treated rats.


CONCLUSIONS
When used in combination with CDDP, VPA displays a protective action against neuropathy, in our models, suggesting possible future clinical applications.
Rodriguez-Menendez
Virginia
V
Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza, Italy.
Gilardini
Alessandra
A
Bossi
Mario
M
Canta
Annalisa
A
Oggioni
Norberto
N
Carozzi
Valentina
V
Tremolizzo
Lucio
L
Cavaletti
Guido
G
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D014635:Valproic Acid; D002945:Cisplatin