Melatonin prevents beta-amyloid-induced lipid peroxidation.
Beta-amyloid is a major constituent of senile plaques that occur in the brains of Alzheimer's disease (AD) patients. Cell culture studies have shown that high concentrations of beta-amyloid are toxic and damage biological macromolecules. A number of experiments have shown that melatonin is a potent antioxidant. Melatonin not only neutralizes oxygen-derived free radicals but can also scavenge species of other types such as carbon-centered free radicals. The present study was designed to determine whether beta-amyloid toxicity would cause lipid peroxidation of human platelet membranes. Since aluminum has been implicated in the etiology of AD, we investigated the effects of aluminum on lipid peroxidation and whether the harmful effects of beta-amyloid are aggravated by aluminum. We also investigated whether melatonin had the ability to protect against beta-amyloid toxicity. Our results indicate that both beta-amyloid and aluminum dose-dependently increased lipid peroxidation in platelet membranes. Aluminum was more potent than beta-amyloid. Incubation of platelet membranes with increasing concentrations of aluminum in the presence of 100 microM beta-amyloid (fragment 25-35) resulted in lipid peroxidation levels of similar magnitude as the two substances, respectively. Prior administration of melatonin dose-dependently inhibited this effect. These results confirm the toxic effects of beta-amyloid to biological membranes. While aluminum itself damages membranes, its presence did not exacerbate the toxic effects of beta-amyloid. Melatonin effectively reduced the lipid peroxidation induced by beta-amyloid and aluminum, suggesting that its supplementation to AD patients may be beneficial.
Daniels
W M
WM
Department of Physiology, University of Stellenbosch, Tygerberg, South Africa.
van Rensburg
S J
SJ
van Zyl
J M
JM
Taljaard
J J
JJ
D000535:Aluminum / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016166:Free Radical Scavengers; D008563:Membrane Lipids; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000535:Aluminum; D008550:Melatonin