The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25-35 in middle-aged rats.
This work investigated the ability of melatonin to prevent oxidative damage in brain tissue induced by injection of beta-amyloid peptide 25-35 (Abeta25-35) in middle-aged rats. The Morris water maze was used to evaluate the cognitive function of the rats. Thiobarbituric acid-reactive substances and antioxidative enzymes (superoxide dismutase and glutathione peroxidase) activities were measured. It was found that injection of (Abeta25-35) (20 microg) into the rat hippocampus caused an increase in the latency (the time to find the platform), the total swimming distance to the platform, and the starting angles in (Abeta25-35)-treated rats. Furthermore, a significant rise in lipid peroxidation and decrease in antioxidative enzyme activities in brain tissue were found. Melatonin (0.1, 1, and 10 mg/kg, i.g. x 10 days) improved the spatial resolution of amnesic rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10 mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic rats, melatonin (0.1, 1.0, and 10 mg/kg. i.g. x 10 days) stimulated the antioxidative enzyme activities. The results show that melatonin effectively reduced lipid peroxidation and enhanced the antioxidative enzyme activities in Abeta(25-35)-treated rats, which may contribute to the improvement of rats' learning and memory impaired by Abeta(25-35).
Shen
Y X
YX
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China. shenyuxi@mail.hf.ah.cn
Xu
S Y
SY
Wei
W
W
Sun
X X
XX
Liu
L H
LH
Yang
J
J
Dong
C
C
D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007267:Injections; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D017392:Thiobarbituric Acid Reactive Substances; C074636:amyloid beta-protein (25-35); D013482:Superoxide Dismutase; D008550:Melatonin