Melatonin prevents β‐amyloid‐induced lipid peroxidation

Abstract

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.

Melatonin protects hippocampal neurons in vivo against kainic acid-induced damage in mice

“…This is a serious problem since many factors such as stress, stroke, air pollution, and food and water contaminated with chemicals mimic the action of KA in generating free radicals. Fortunately, melatonin shows a direct function in protecting against A␤-induced lipid peroxidation and cell damage in different cell cultures Daniels et al, 1998). Thus, melatonin may be capable of breaking the cycle referred to previously.…”

The Oxidant/Antioxidant Network: Role of Melatonin

“…This observation, however, has been question by several later workers [24]. Thus, while melatonin is highly protective against induced lipid peroxidation [25][26][27], there is a question whether this protective effect of melatonin is a consequence of LOO W scavenging or via some secondary means, e.g., stabilization of cell membranes permitting them to resist oxidative damage [28].…”

“…Some of the organs in which these protective effects have been shown include the gastrointestinal tract and adnexa [25,[39][40][41][42], central nervous system [2,[43][44][45][46][47], eye [48,49], kidneys [42,50], heart [51,52], blood elements [27,53], lungs [54] and muscle [55]. The macromolecules that have been most often studied in terms of the protective actions of melatonin include lipids [6, 25-27, 36-38, 42, 48, 49, 54-56] and nuclear DNA [6, 10, 36-38, 53, 57, 58].…”

Nutritional Factors in Cerebral Aging and Dementia: Epidemiological Arguments for a Role of Oxidative Stress

“…There is evidence that oxidative stress might be directly involved in the development of the senile plaque, the hallmark lesion of AD [56]. The relation between deposition of ß-amyloid peptide and the oxidative stress in AD was shown in several studies [85][86][87]. The Aß protein might represent the molecular link between oxidative stress and neuronal death in this disease [88].…”