ascorbic-acid and 6-methoxytryptoline

The serum concentrations of aluminum, a metal potentially involved in the pathogenesis of Alzheimer's disease, increase with age. Also, intense and prolonged exposure to aluminum may result in dementia. Melatonin and pinoline are two well known antioxidants that efficiently reduce lipid peroxidation due to oxidative stress. Herein, we investigated the effects of melatonin and pinoline in preventing aluminum promotion of lipid peroxidation when the metal was combined with FeCl3 and ascorbic acid in rat synaptosomal membranes. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations in the membrane suspension. Under the experimental conditions used herein, the addition of aluminum (0.0001 to 1 mmol/L) enhanced MDA + 4-HDA formation in the synaptosomes. Melatonin and pinoline reduced, in a concentration-dependent manner, lipid peroxidation due to aluminum, FeCl3 and ascorbic acid in the synaptosomal membranes. These results suggest that the indoleamine melatonin and the beta-carboline pinoline may potentially act as neuroprotectant agents in the therapy of those diseases with elevated aluminum concentrations in the tissues.

Topics: Alkenes; Aluminum; Animals; Anticonvulsants; Ascorbic Acid; Carbolines; Dose-Response Relationship, Drug; Free Radical Scavengers; Iron; Lipid Peroxidation; Malondialdehyde; Melatonin; Rats; Rats, Sprague-Dawley; Synaptosomes

Tryptoline and pinoline are two beta-carbolines isolated from the nervous system of mammals. We investigated the ability of these compounds to prevent lipid peroxidation induced by hydrogen peroxide in rat brain homogenates. We also compared their effects with other known antioxidants including melatonin, trolox and ascorbic acid. Lipid peroxidation was assessed by measuring malonaldehyde (MDA) and 4-hydroxy-alkenals (4-HDA) concentrations in the brain homogenates. Incubation with hydrogen peroxide (5 mM) increased MDA+4-HDA levels, which were totally prevented by tryptoline, pinoline, melatonin and trolox in a concentration-dependent manner. By contrast, higher MDA-4-HDA concentrations compared with control experiments were found after incubation with ascorbic acid, thus reflecting an increase of lipid peroxidation induced by this compound. Although in vivo studies are needed, the data suggest that these beta-carbolines may be potential neuroprotective agents because of their antioxidant activities.

Topics: Aldehydes; Animals; Antioxidants; Ascorbic Acid; Brain Chemistry; Carbolines; Cell-Free System; Chromans; Dose-Response Relationship, Drug; Hydrogen Peroxide; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Rats; Rats, Sprague-Dawley