Clinical And Experimental Study Of Shen Fu Injection Alleviating Paclitaxel-Induced Peripheral Neurotoxicity

Objective To investigate the effects and underlying mechanisms of ShenFu Injection alleviating paclitaxel-induced peripheral neurotoxicity by clinical and animal study.Method 1)Clinical Study : 67 patients were divided into two groups: 32 patients were enrolled in control group which was treated with chemotherapy alone,35 patients were enrolled in experiment group that the Shenfu injection was used in the same period of chemotherapy at the dose of 100ml/d.Chemotherapy regimens included paclitaxel.Inspecting patients' serum NGF content in each group before chemotherapy,Peripheral neurotoxicity was assessed after 2 and 4 cycles of chemotherapy treatment,and detected NGF level at the same time.Chemotherapy-related side effects were recorded during the period of chemotherapy.2)Animal Study : Twenty-eight adult male Wister rats were randomized into 4 groups(n=7): control group;paclitaxel group;paclitaxel combined with low and high dose of ShenFu Injection groups.Each group was intraperitoneally injected paclitaxel 8mg/kg at day 1,5,9,13 except control group.Low and high dose of ShenFu Injection groups were daily intraperitoneally injected ShenFu Injection4mL/kg,8mL/kg respectively,3 weeks in total.Control group was continuously intraperitoneally injected NS with same volume every day for 3 weeks.Mechanical Withdraw Threshold(MWT)and Thermal Withdraw Latency(TWL)of rats' hind paw were mesured at day 0,6 and 14.Executed the rats the next day after the last injection of ShenFu Injection.The ultrastructure of the sciatic nerve was observed with transmission electron microscope and the value of nerve growth factor(NGF)in the serum was measured.Results 1)Clinical Study : The occurrence rates of peripheral neurotoxicity in experimental group,control group were 22.86% and 37.5% respectively after 2 cycles of the treatment(P>0.05),31.43%,53.15% after 4 cycles(P<0.05).Serum NGF content in experimental group,control group were 42.22ng/L,41.8ng/L respectively before chemotherapy,and 37.68ng/L,34.87ng/L respectively after 2 cycles treatment(P>0.05),after 4 cycles at 40.6ng/L and 29.57ng/L respectively(P<0.05).During the period of chemotherapy,there were no significant differences about the incidence rate of chemotherapy-related side effects such as nausea,vomit,diarrhea,neutropenia and anemia between experimental group and control group(P>0.05).The incidence rate of neutropenia were 22.86%,34.38% respectively(P>0.05).2)Animal Study : The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group(P<0.05).While compared paclitaxel with Shenfu Injection especially the high dose(P<0.05)significantly reduced.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 Shenfu Injection group(P>0.05).When compare to control group,the sciatic nerve fiber structure in paclitaxel group was generally damaged,including myelin sheath swelling,fragmentation and vacuolization,heavily endoplasmic reticulum swelling,mitochondria damaging and matrix structure disorder in Schwann cells.The structure damages were mitigated in the low and high dose groups,especially the latter one,when compared to the paclitaxel group.Compared with control group,the serum NGF level significantly decreased(P<0.05)in the paclitaxel group.While the serum NGF level in low and high dose of Shenfu Injection groups were higher than paclitaxel group,particularly in high dose group(P<0.05).Conclusion ShenFu Injection can reduce the peripheral neurotoxicity of paclitaxel,remarkably with high dose.To sustain the complete structure of peripheral nerves is one of the potential mechanisms,which is associated with the increased expression of NGF in serum.