Preventive effect of PC-SOD on oxaliplatin-induced peripheral neuropathy in rats

Abstract Oxaliplatin is widely used as a chemotherapeutic agent for treating various cancers, including colorectal cancer. However, oxaliplatin-induced peripheral neuropathy diminishes the quality of life of patients and leads to a reduction in the chemotherapy dose or even early discontinuation. Thus, the development of preventive or therapeutic drugs for oxaliplatin-induced peripheral neuropathy is urgently needed and may enhance its therapeutic effect. Herein, we aimed to investigate whether PC-SOD, a derivative of SOD with higher stability in the plasma and higher affinity for tissues, could prevent oxaliplatin-induced peripheral neuropathy. A neurite outgrowth assay using cultured PC12 cells and a rat model of oxaliplatin-induced peripheral neuropathy were used to elucidate the neuroprotective effects of PC-SOD. PC-SOD effectively attenuated oxaliplatin-induced neurite damage in cultured PC12 cells. In a rat model, PC-SOD reduced oxaliplatin-induced mechanical allodynia, cold hyperalgesia, and morphological damage to intraepidermal nerve fibres and dorsal root ganglion. Furthermore, PC-SOD did not affect the anti-tumour effects of oxaliplatin in cultured tumour cells or in tumour cell-implanted mice. These findings indicated that PC-SOD alleviated oxaliplatin-induced mechanical allodynia, cold hyperalgesia, and neural damage without affecting the antitumor activity of oxaliplatin. Therefore, PC-SOD is a promising drug candidate for the prevention of oxaliplatin-induced peripheral neuropathy.