الفهرس | Only 14 pages are availabe for public view |
Abstract Chemotherapy-induced peripheral neuropathy is one of the most distressing side effects of chemotherapeutic drugs. In this study we tried to investigate the effect of NGF and ATRA on peripheral neuropathy induced by chemotherapeutic drug, taxol. In this work, 70 adult male albino rats were used. They were classified into 6 groups (G). G1, normal control (n= 10), G2 model control group (n=20), IP injected with taxol (2mg/kg) on days 1, 3, 5, and 7. G3, G4, G5, G6 (n of each=10), G3 was IP injected with rhNGF (10ug/kg daily for 2 weeks) one hour before taxol injection. G4 was IP injected with rhNGF (10ug/kg daily for 2 weeks) after one week from the last dose of taxol injection. G5 was IP injected with ATRA (20mg/kg daily for 2 weeks) after one week from the last dose of taxol injection.G6 was IP injected with both rhNGF and ATRA (10ug/kg, 20mg/kg respectively) daily for 2 weeks after one week from the last dose of taxol injection. In this work, the collected data were statistically analyzed using Statistical Package Social Science (SPSS) version 16. Comparison between groups after the treatment was examined by using unpaired t-test. P<0.05 was considered statistically significant. In this study taxol injection resulted in significant decrease in SSNCV and CMNCV, also it resulted in significant prolongation of thermal pain threshold. In addition, there were myelinopathy and axonapathy in the examined sections of sciatic nerve in taxol treated rats. These changes were improved by the use of rhNGF and ATRA. In G3, G4, G5, there was some improvement in the low levels of SSNCV, CMNCV and the prolongation of thermal pain threshold induced by taxol. However they were still statistically significant compared to normal control group. In histological examination of G3, G4, G5, there was some improvement in the neuropathic changes. Furthermore, the mean axon diameter of the myelinated sciatic nerve fiber and perimeter were statistically insignificant compared to normal control group. In G6, there was marked improvement in the low levels of SSNCV, CMNCV and the prolongation of thermal pain threshold induced by taxol as they were statistically insignificant compared to normal control group. In addition, histological examination showed marked improvement in the neuropathic changes of G6. The mean axon diameter of the myelinated sciatic nerve fibers and perimeter were statistically insignificant compared to normal control group. Conclusion: In this work, neither injection of NGF alone or ATRA alone was able to return SSNCV, CMNCV and thermal pain threshold or histological finding back to normal as manifested by statistically significant decrease in SSNCV, CMNCV and increased thermal pain threshold compared to normal control group. In addition, the therapeutic effects of NGF and ATRA were statistically insignificant from each other. The combined injection of both NGF and ATRA revealed marked improvement in SSNCV, CMNCV, thermal pain threshold and histological findings as proved by statistically insignificant change from the normal control group. Recommendations: We recommend that patients receiving chemotherapeutic drugs should receive both NGF and ATRA for prevention and treatment of chemotherapy induced peripheral neuropathy. Further studies should be done in animals already having cancer to detect if the use of NGF in combination with ATRA can affect the antitumor efficacy of chemotherapeutic drugs or not. |