Acetyl-L-Carnitine prevents and reverts experimental chronic neurotoxicity induced by oxaliplatin, without altering its antitumor properties.
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.
Ghirardi
Orlando
O
Research and Development, Sigma-Tau S.p.A. Industrie Farmaceutiche Riunite, Rome, Italy. orlando.ghirardi@sigma-tau.it
Lo Giudice
Pietro
P
Pisano
Claudio
C
Vertechy
Mario
M
Bellucci
Augusta
A
Vesci
Loredana
L
Cundari
Sante
S
Miloso
Mariarosaria
M
Rigamonti
Laura Maria
LM
Nicolini
Gabriella
G
Zanna
Claudio
C
Carminati
Paolo
P
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
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000108:Acetylcarnitine