title: Acetyl-L-Carnitine prevents and reverts experimental chronic neurotoxicity induced by oxaliplatin, without altering its antitumor properties.
abstract: BACKGROUND
  Oxaliplatin (OHP) is severely neurotoxic and induces the onset of a disabling sensory peripheral neuropathy. Acetyl-L-carnitine (ALC), a natural compound with neuroprotective action, was tested to determine whether it plays a protective role in OHP-induced neuropathy.
  
  
  METHODS
  Peripheral neuropathy was induced in Wistar rats, and the effect of OHP alone or in combination with ALC was assessed, using behavioral and neurophysiological methods. Moreover, ALC interference on OHP antitumor activity was investigated using several in vitro and in vivo models.
  
  
  RESULTS
  ALC-co-treatment reduced the neurotoxicity of OHP when it was coadministered. Furthermore, the administration-of OHP, once OHP-induced neuropathy was established, significantly mitigated its severity. Finally, experiments in different tumor systems indicated that ALC does not interfere with the antitumor effects of OHP.
  
  
  CONCLUSIONS
  ALC is effective in the prevention and treatment of chronic OHP-induced peripheral neurotoxicity in an experimental rat model.
authors.affiliation: Research and Development, Sigma-Tau S.p.A. Industrie Farmaceutiche Riunite, Rome, Italy. orlando.ghirardi@sigma-tau.it
authors.forename: Orlando
authors.initials: O
authors.lastname: Ghirardi
authors.forename: Pietro
authors.initials: P
authors.lastname: Lo Giudice
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.forename: Mario
authors.initials: M
authors.lastname: Vertechy
authors.forename: Augusta
authors.initials: A
authors.lastname: Bellucci
authors.forename: Loredana
authors.initials: L
authors.lastname: Vesci
authors.forename: Sante
authors.initials: S
authors.lastname: Cundari
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Miloso
authors.forename: Laura Maria
authors.initials: LM
authors.lastname: Rigamonti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nicolini
authors.forename: Claudio
authors.initials: C
authors.lastname: Zanna
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002908:Chronic Disease; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology*; D000077150:Oxaliplatin; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000108:Acetylcarnitine