Alpha-lipoic acid and epalrestat prevents the defects of sensory nerves and mechanosensory cells on oxaliplatin-induced peripheral neuropathy in zebrafish

초록

Background and aims: Oxaliplatin is a platinum-based chemotherapy drug widely used in colorectal cancer patients. Although it frequently causes oxaliplatin-induced peripheral neuropathy (OIPN) in 80 % of patients with colorectal cancer with neuropathic pain and loss of sensation, appropriate treatments to effectively prevent OIPN are currently very limited. The aim of this study was to evaluate and uncover mechanism of preventive effects of alpha-lipoic acid (ALA) and epalrestat (EP) in OIPN zebrafish model. Methods: Tg(tubb2b:dsred) and Tg(brn3c:gfp) transgenic zebrafish, with sensory nerves in the peripheral lateral line (PLL) and mechanosensory hair cells (MHCs) in neuromast respectively, were treated with Oxaliplatin(Oxali), Oxali/ALA, and Oxali/EP for 4 days. A confocal microscope (Nikon A1) was used to acquire images of histological preparations. And then, the number of axon bifurcation and MHCs of PLL nerve were quantified by using NIS-Element (Nikon). Results: We observed that the number of axon bifurcation and MHCs were significantly reduced in the Oxali-treated group compared with those in the control group. In both the Oxali/ALA and Oxali/EP groups, the number of axon bifurcation and MHCs were greater than Oxali-treated group. No significant difference was observed between Oxali/ALA and Oxali/EP. Conclusions: These data indicate that ALA and EP have prevention effects to OIPN in the zebrafish. These findings show that ALA and EP can provide more beneficial effects to OIPN treatment.