Among people aged 65 and older, higher ascorbic acid and beta-carotene plasma level are associated with better memory performance. These results indicate the important role played by antioxidants in brain aging and may have implications for prevention of progressive cognitive impairments.
Abstract:Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl 2 ) on oxidative stress, cell cytotoxicity, -amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 g/L (180 nM) HgCl 2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n ϭ 13, p Ͻ 0.001). Preincubation of cells for 30 min with 1 M melatonin or premixing melatonin and HgCl 2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MT T ) cytotoxicity assays revealed that 50 g/L HgCl 2 for 24 h produced a 50% inhibition of MT T reduction (n ϭ 9, p Ͻ 0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MT T reduction equaling control levels. The release of -amyloid peptide (A) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl 2 was shown to be different: A 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas A 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n ϭ 9, p Ͻ 0.001). Preincubation of cells with melatonin resulted in an attenuation of A 1-40 and A 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n ϭ 9, p Ͻ 0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD. Key Words: Mercury-Oxidative stress--Amyloid-TauMelatonin-SHSY5Y neuroblastoma cells.
Previous cross-cultural comparisons of the mortality from ischemic heart disease in European communities with associated plasma levels of essential antioxidants have revealed strong inverse correlations for vitamin E and relatively weak correlations for other antioxidants. Similarly, in a case-control study in Edinburgh low plasma levels of vitamin E were significantly associated with an increased risk of previously undiagnosed angina pectoris whereas low levels of other essential antioxidants lacked statistical significance. The current Basel Prospective Study is particularly well suited to elucidate the impact of antioxidants other than vitamin E. In this population (which was recently evaluated regarding cancer mortality) the plasma levels of vitamins E and A are exceptionally high and above the presumed threshold level of risk for ischemic heart disease. The present 12-year follow-up of cardiovascular mortality in this study reveals a significantly increased relative risk of ischemic heart disease and stroke at initially low plasma levels of carotene (< 0.23 mumol/l) and/or vitamin C (< 22.7 mumol/l), independently of vitamin E and of the classical cardiovascular risk factors. Low levels of both carotene and vitamin C increase the risk further, in the case of stroke even with significance for overmultiplicative interaction. In conclusion, in cardiovascular disease independent inverse correlations may exist for every major essential antioxidant although the latter can also interact synergistically. Therefore future intervention trials of antioxidants in the prevention of ischemic heart disease should primarily test the simultaneous optimization of the status of all principal essential antioxidants.
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