The distribution of aluminum into and out of the brain

Yokel, Robert A.; Allen, David; Ackley, David C.

doi:10.1016/s0162-0134(99)00124-5

Cited by 89 publications

(50 citation statements)

References 27 publications

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“…Aluminium may enter the brain through multiple routes: from blood, either through choroid plexus or across the blood brain barrier (BBB) and from the nasal cavity into olfactory nerves, followed by direct distribution into the brain (73) . The large size (about 77,000 Da) and low ipophilicity of transferrin preclude its ability to diffuse through the pericellular pathway or endothelial cell membrane (74) . The transport both of essential and non-essential metal ions across membrane barriers, such as the bloodbrain barrier, is mediated by specific transport mechanisms that regulate the brain levels of different metals (75) .…”

Section: Brain Pathologymentioning

confidence: 99%

The meaning of aluminium exposure on human health and aluminium-related diseases

Crisponi

Fanni²,

Gerosa³

et al. 2013

BioMolecular Concepts

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Abstract:The aim of this review is to attempt to answer extremely important questions related to aluminiumrelated diseases. Starting from an overview on the main sources of aluminium exposure in everyday life, the principal aspects of aluminium metabolism in humans have been taken into consideration in an attempt to enlighten the main metabolic pathways utilised by trivalent metal ions in different organs. The second part of this review is focused on the available evidence concerning the pathogenetic consequences of aluminium overload in human health, with particular attention to its putative role in bone and neurodegenerative human diseases.

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Section: Brain Pathologymentioning

confidence: 99%

The meaning of aluminium exposure on human health and aluminium-related diseases

Crisponi

Fanni²,

Gerosa³

et al. 2013

BioMolecular Concepts

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“…The possible role of Al in AD rises the important question whether Al can enter the brain, and if it does, which is (are) the mechanism(s) of entry? For it, three routes have been proposed: blood-brain barrier (BBB), nasal olfactory pathway, and cerebrospinal fluid (CSF) (Yokel et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum

et al. 2009

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It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimer's disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AbetaPP female transgenic (Tg2576) (Tg) and wild-type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu-ZnSOD, GR, and CAT was evaluated by real-time RT-PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro-oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model.

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“…Stable organic complexes of Al (e.g., oxalate or citrate) seem to mitigate the toxic effects on methanotroph activity (25) and root growth (13). However, citrate complexes also seem to be the mechanism by which soluble Al crosses the blood-brain barrier (46). With respect to inorganic forms of Al, most studies suggest that monomeric Al 3ϩ is the actively toxic species, even though toxicity seems to peak in the slightly acidic to neutral region (pH 5 to 6.5) rather than at lower pHs, where Al 3ϩ dominates (e.g., see reference 6).…”

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confidence: 99%

Toxicity of Al to Desulfovibrio desulfuricans

Amonette

Russell

Carosino

et al. 2003

Appl Environ Microbiol

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The toxicity of Al to Desulfovibrio desulfuricans G20 was assessed over a period of 8 weeks in a modified lactate C medium buffered at four initial pHs (5.0, 6.5, 7.2, and 8.3) and treated with five levels of added Al (0, 0.01, 0.1, 1.0, and 10 mM). At pH 5, cell population densities decreased significantly and any effect of Al was negligible compared to that of the pH. At pHs 6.5 and 7.2, the cell population densities increased by 30-fold during the first few days and then remained stable for soluble-Al concentrations of <5 ؋ 10 ؊5 M. In treatments having total-Al concentrations of >1 mM, soluble-Al concentrations exceeded 5 ؋ 10 ؊5 M and limited cell population growth substantially and proportionally. At pH 8.3, soluble-Al concentrations were below the 5 ؋ 10 ؊5 M toxicity threshold and cell population density increases of 20-to 40-fold were observed. An apparent cell population response to added Al at pH 8.3 was attributed to the presence of large, spirilloidal bacteria (accounting for as much as 80% of the cells at the 10 mM added Al level). Calculations of soluble-Al speciation for the pH 6.5 and 7.2 treatments that showed Al toxicity suggested the possible presence of the Al 13 O 4 (OH) 24 (H 2 O) 12 7؉ "tridecamer" cation and an inverse correlation of the tridecamer concentration and the cell population density. Analysis by 27 Al nuclear magnetic resonance spectroscopy, however, yielded no evidence of this species in freshly prepared samples or those taken 800 days after inoculation. Exclusion of the tridecamer species from the aqueous speciation calculations at pHs 6.5 and 7.2 yielded inverse correlations of the neutral Al(OH) 3 and anionic Al(OH) 4 ؊ monomeric species with cell population density, suggesting that one or both of these ions bear primary responsibility for the toxicity observed.Aluminum, the most abundant metal and the third most abundant element in the earth's crust (37), finds surprisingly little use in biological systems. Although the inherent chemistry of Al certainly is a factor, the chemical conditions existing on the earth at the time the earliest organisms were developing may also have played a role (42, 43). These conditions, which include neutral pH and the absence of oxygen, were such that the solubility of Al was minimal relative to that of divalent metals such as Mg, Ca, and Fe(II). Even if availability were not limiting, however, several other chemical properties of Al strongly militate against its use in cellular metabolism (5). The inherently slow rate of inner-sphere ligand exchange for Al 3ϩ (10 5 to 10 8 times slower than for Mg 2ϩ , Ca 2ϩ , or Fe 2ϩ [41]) makes its complexes relatively inert. Further inertness stems from the lack of any electron transfer chemistry. Moreover, Al 3ϩ forms complexes with greater thermodynamic stability than that of those formed by the divalent metals because of its smaller size and higher valence. Thus, the ability of Al to form strong, relatively inert complexes not only prevents its use by the cyclic feedback-regulated processes in cellu...

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The distribution of aluminum into and out of the brain

Cited by 89 publications

References 27 publications

The meaning of aluminium exposure on human health and aluminium-related diseases

The meaning of aluminium exposure on human health and aluminium-related diseases

Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum

Toxicity of Al to Desulfovibrio desulfuricans

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