Peripheral nerve injury (PNI) produces functional changes in lesioned neurons in which oxidative stress is considered to be the main cause of neuronal damage. As
superoxide dismutase (SOD) is an important antioxidative
enzyme involved in redox regulation of oxidative stress, the present study determined whether
melatonin would exert its beneficial effects by preserving the SOD reactivity following PNI. Adult rats subjected to
hypoglossal nerve transection were intraperitoneally injected with
melatonin at ones for 3, 7, 14, 30 and 60 days successively. The potential
neuroprotective effects of
melatonin were quantitatively demonstrated by
neuronal nitric oxide synthase (nNOS), mitochondrial
manganese SOD (
Mn-SOD), and cytosolic
copper-
zinc SOD (Cu/Zn-SOD) immunohistochemistry. The functional recovery of the lesioned neurons was evaluated by
choline acetyltransferase (ChAT) immunohistochemistry along with the electromyographic (EMG) recordings of
denervation-induced fibrillation activity. The results indicate that following PNI, the nNOS immunoreactivity was significantly increased in lesioned neurons peaking at 14 days. The up-regulation of nNOS temporally coincided with the reduction of ChAT and SOD in which the Cu/Zn-SOD showed a greater diminution than
Mn-SOD. However, following
melatonin administration, the nNOS augmentation was successfully suppressed and the activities of
Mn-SOD, Cu/Zn-SOD, and ChAT were effectively preserved at all postaxotomy periods. EMG data also showed a decreased fibrillation in
melatonin-treated groups, suggesting a potential effect of
melatonin in promoting functional recovery. In association with its significant capacity in preserving SOD reactivity,
melatonin is suggested to serve as a powerful therapeutic agent for treating PNI-relevant oxidative damage.