Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel

Objective To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. Methods Twenty-eight adult male Wister rats were randomized into 4 groups （n=7）: control group，paclitaxel group，paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection), low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively, while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL） of rats’ hind paw were measured before (0 d) and after the first injection (6 d, 14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia, and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. Results The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group (P<0.05). The combination of paclitaxel with ShenFu Injection, especially the high dose (P<0.05), significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group, there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection （P＞0.05）. Compared with control group, the serum NGF level significantly decreased （P<0.05） in paclitaxel group, while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group, particularly in the high dose group (P<0.05). When compared to control group, the sciatic nerve fiber structure in the paclitaxel group was generally damaged, including myelin sheath swelling, fragmentation and vacuolization, endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups, especially the latter one, when compared to the paclitaxel group. Conclusion Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.