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. Materials and 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. Conclusion: ALC is effective in the prevention and treatment of chronic OHP-induced peripheral neurotoxicity in an experimental rat model.