title: Valproate protective effects on cisplatin-induced peripheral neuropathy: an in vitro and in vivo study.
abstract: 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.
authors.affiliation: Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Rodriguez-Menendez
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gilardini
authors.forename: Mario
authors.initials: M
authors.lastname: Bossi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Canta
authors.forename: Norberto
authors.initials: N
authors.lastname: Oggioni
authors.forename: Valentina
authors.initials: V
authors.lastname: Carozzi
authors.forename: Lucio
authors.initials: L
authors.lastname: Tremolizzo
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
mesh_terms: 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*
chemical_list: D014635:Valproic Acid; D002945:Cisplatin