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

Abstract

BACKGROUND: 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. Thus, the development of preventive or therapeutic drugs for oxaliplatin-induced peripheral neuropathy is urgently needed. Herein, we aimed to investigate whether PC-SOD, a derivative of SOD with higher stability in plasma and higher affinity for tissues, could prevent oxaliplatin-induced peripheral neuropathy. RESULTS: PC-SOD significantly attenuated oxaliplatin-induced neurite damage and reduced oxaliplatin-induced reactive oxygen species (ROS) production in cultured PC12 cells. In a rat model, PC-SOD reduced oxaliplatin-induced mechanical allodynia, cold hyperalgesia, and morphological damage to intraepidermal nerve fibers and dorsal root ganglion. Furthermore, PC-SOD did not significantly affect the antitumor effects of oxaliplatin in cultured tumor cells or in tumor cell-implanted mice. CONCLUSION: These findings indicated that PC-SOD alleviated oxaliplatin-induced mechanical allodynia, cold hyperalgesia, and neural damage without significantly affecting the antitumor activity of oxaliplatin. Therefore, PC-SOD is a promising drug candidate for the prevention of oxaliplatin-induced peripheral neuropathy.