Melatonin mitigates oxidative damage and apoptosis in mouse cerebellum induced by high-LET 56Fe particle irradiation.
Cerebellum is a vital organ responsible for the motor coordination and recently it has been reported to be involved in cognitive function. Reactive oxygen species are implicated in neurodegeneration and cognitive disorders because of higher vulnerability of neuronal tissues. Therefore, the present study aimed at investigating the role of melatonin against high-LET (linear energy transfer) (56)Fe particle irradiation-induced oxidative damage and apoptosis in the mouse cerebellum. Radiation-induced oxidative damage was examined using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL), quantitative histopathology, DNA damage (comet assay), carbonyl content and 4-HAE + MDA (4-hydroxyalkenal + malondialdehyde) status of the cerebellum. Radiation exposure augmented the number of TUNEL positive cell, DNA migration in the comet tail and carbonyl and 4-HAE + MDA level in the cerebellum. Melatonin pretreatment significantly inhibited the oxidative damage to biomolecules as well as cerebellar apoptosis. Melatonin-treated irradiated mice showed higher counts of intact Purkinje cells as compared to vehicle-treated irradiated mice. In addition, radiation induced augmentation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and a decline in the total antioxidant capacity in serum; these changes were also ameliorated by melatonin pretreatment. The present results provide evidence supporting the antioxidant and neuroprotective function of melatonin.
Manda
Kailash
K
National Institute of Radiological Sciences, Chiba, Japan.
Ueno
Megumi
M
Anzai
Kazunori
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D002526:Cerebellar Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007501:Iron / Q000009:adverse effects*; D018499:Linear Energy Transfer / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010316:Particle Size
D007501:Iron; D008550:Melatonin