Melatonin Ameliorates Radiation-induced Sciatic Nerve Injury

Abstract

Background: Radiotherapy is a treatment method for cancer mostly utilized for about 60% of cancer patients. Peripheral neuropathy is one of the severe complications of radiotherapy. Two stages of neuropathy will occur following irradiation; electrophysiological and biochemical variations as the first stage, while the second stage involves fibrosis of soft tissues surrounding the exposed nerve. This novel study aimed to investigate the radioprotective effects of melatonin against ionizing radiation-induced sciatic nerve damage. Methods: 60 rats were randomly assigned to four groups; C (Control), M (Melatonin), R (Radiation), MR (Radiation + Melatonin). Their right legs were exposed to 30 Gy single dose gamma rays. Melatonin (100 mg/kg) was administered 30 min before irradiation and once daily (5 mg/kg) till the day of rats’ sacrifice. Their exposed nerve tissues were evaluated for biochemical changes in addition to Electromyography (EMG) and Nerve Conduction Study (NCS). Results: 4, 12 and 20 weeks post-irradiation, EMG and NCS examinations in R group showed reduced Compound Muscle Action Potential (CMAP) representing axonal degeneration when compared with C and M groups. Prolonged latency and a decrease in Conduction Velocity (CV) gave an indication of demyelinating neuropathy at 12 and 20 weeks. EMG and NCS results of R group showed partial nerve lesion. Biochemical assessments showed that irradiation of sciatic nerve led to increased MDA level, as well as decreased CAT and SOD activities. However, in all cases, treatment with melatonin can reverse these effects. Conclusion: We conclude that melatonin can improve electrophysiological, oxidative stress and antioxidant defense features of irradiated rats’ sciatic nerves. We would also recommend the use of melatonin in an optimal and safe dose. It should be administered over a long period of time for effective protection of the peripheral nerve tissues, as well as improving the therapeutic ratio of radiotherapy.