Melatonin attenuates MPTP-induced dopaminergic neuronal injury associated with scavenging hydroxyl radical.
To clarify the relationship between melatonin's hydroxyl radical (*OH) scavenging ability and its protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, in the present study, the salicylate trapping method combined with high-performance liquid chromatography (HPLC)-electrochemical detection were used to measure the contents of dihydroxybenzoic acid (DHBA) and dopamine (DA) in brain tissues of C57BL/6 mice. Immunocytohistochemistry was used to detect tyrosine hydroxylase (TH)-like positive staining neurons. Results show that MPTP treatment induced an increase in the content of DHBA and decrease in the level of DA as well as the number of TH positive stained neurons in the mouse brain. However, melatonin dose-dependently inhibited the increase of DHBA levels in ventral midbrain tissues, the decrease of DA content and the loss of dopaminergic neurons. Moreover, the relationship between the changes of DHBA and DA levels in the brain of mice following MPTP and melatonin treatment showed a statistically significant negative correlation. Present results suggest that melatonin can ameliorate MPTP-induced dopaminergic neuronal lesions probably, at least partially, because of its inhibition of *OH generation.
Li
Xue-June
XJ
National Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, Shanghai, China.
Gu
Jing
J
Lu
Shi-Duo
SD
Sun
Feng-Yan
FY
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005841:Gentisates; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine