Aluminum chelation: Chemistry, clinical, and experimental studies and the search for alternatives to desferrioxamine

Yokel, Robert A.

doi:10.1080/15287399409531834

Cited by 75 publications

(33 citation statements)

References 199 publications

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“…DE consists of an abnormal accumulation of Al in the brain of uremic patients with renal failure undergoing chronic dialysis, which occurs when tap water, without any further purification, was used in the dialysis process (Zatta et al 2004;Zatta 2006). The effects of Al on cognitive functions were reversible since DE patients greatly improved following treatment with desferrioxamine (DFO) (Yokel 1994). Once Al was removed from the ''dialysis bath'' the DE practically disappeared.…”

Section: Aluminummentioning

confidence: 98%

Metal Ion Physiopathology in Neurodegenerative Disorders

2009

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Metal dyshomeostasis in the brain (BMD) has often been proposed as a possible cause for several neurodegenerative disorders (NDs). Nevertheless, the precise nature of the biochemical mechanisms of metal involvement in NDs is still largely unknown. Mounting evidence suggests that normal aging itself is characterized by, among other features, a significant degree of metal ion dysmetabolism in the brain. This is probably the result of a progressive deterioration of the metal regulatory systems and, at least in some cases, of life-long metal exposure and brain accumulation. Although alterations of metal metabolism do occur to some extent in normal aging, they appear to be highly enhanced under various neuropathological conditions, causing increased oxidative stress and favoring abnormal metal-protein interactions. Intriguingly, despite the fact that most common NDs have a distinct etiological basis, they share striking similarities as they are all characterized by a documented brain metal impairment. This review will primarily focus on the alterations of metal homeostasis that are observed in normal aging and in Alzheimer's disease. We also present a brief survey on BMD in other NDs (Amyotrophic Lateral Sclerosis, Parkinson's, and Prion Protein disease) in order to highlight what represents the most reliable evidence supporting a crucial involvement of metals in neurodegeneration. The opportunities for metal-targeted pharmacological strategies in the major NDs are briefly outlined as well.

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Section: Aluminummentioning

confidence: 98%

Metal Ion Physiopathology in Neurodegenerative Disorders

2009

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“…These results support the idea that PAs may perturb the Al binding to root cells through complex formation. The monomeric catechin, one of the major PA components, has a higher stability constant for Al than the catechin dimer (Yokel, 1994;Barceló and Poschenrieder, 2002). PAs can form complexes with Al, depending on the degree of polymerization and the number of hydroxyl bases (Yoneda and Nakatsubo, 1998).…”

Section: Discussionmentioning

confidence: 99%

Transient Proliferation of Proanthocyanidin-Accumulating Cells on the Epidermal Apex Contributes to Highly Aluminum-Resistant Root Elongation in Camphor Tree

et al. 2010

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Aluminum (Al) is a harmful element that rapidly inhibits the elongation of plant roots in acidic soils. The release of organic anions explains Al resistance in annual crops, but the mechanisms that are responsible for superior Al resistance in some woody plants remain unclear. We examined cell properties at the surface layer of the root apex in the camphor tree (Cinnamomum camphora) to understand its high Al resistance mechanism. Exposure to 500 mM Al for 8 d, more than 20-fold higher concentration and longer duration than what soybean (Glycine max) can tolerate, only reduced root elongation in the camphor tree to 64% of the control despite the slight induction of citrate release. In addition, Al content in the root apices was maintained at low levels. Histochemical profiling revealed that proanthocyanidin (PA)-accumulating cells were present at the adjacent outer layer of epidermis cells at the root apex, having distinctive zones for cell division and the early phase of cell expansion. Then the PA cells were gradually detached off the root, leaving thin debris behind, and the root surface was replaced with the elongating epidermis cells at the 3-to 4-mm region behind the tip. Al did not affect the proliferation of PA cells or epidermis cells, except for the delay in the start of expansion and the accelerated detachment of the former. In soybean roots, the innermost lateral root cap cells were absent in both PA accumulation and active cell division and failed to protect the epidermal cell expansion at 25 mM Al. These results suggest that transient proliferation and detachment of PA cells may facilitate the expansion of epidermis cells away from Al during root elongation in camphor tree.

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“…Desferrioxa n m c (deferoxamine) has been the most used chelator in eliniin:tting excess of A1 after its absorption. This drug has been hewn to be effective in the treatment of dialysis-associaled Al disease and Al-related osteomalacia (Yokel 1994: Nieboer et al 1995Yokel et a/. 1996a).…”

mentioning

confidence: 99%

Aluminium Distribution and Excretion: A Comparative Study of a Number of Chelating Agents in Rats

Gómez

Esparza

Domingo

et al. 1998

Pharmacology & Toxicology

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Ahsitwt: The present study was conducted to assess in rats the comparative effects of a number of chelating agents on the urinary excretion and tissue distribution of Al. Adult male Spraguc-Dawley rats received a single intraperitoneal dose of aluminium (Al) nitrate nonahydrdte (0.24 mmol/kg). Ten min. after A1 injection, 1.2-dimethyl-3-hydroxypirid-4-one, 2,3-dihydroxybenzoic acid, picolinic acid, methylmalonic acid, ethylenediamine-di(o-hydroxyphenylacetic) acid. l-benzyl-2-methyl-3-hydroxypyrid-4-one. I-@-methylbenzyI)-2-methyl-3-hydroxypyrid-4-one, I-@-methoxy-benzyl)-2-methyl-3-hydroxypyrid-4-one, I-@-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one~ I-benzyl-2-ethyl-3-hydroxypyrid-4-one, I-@-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one, l-[3-hydroxy-2-methyI-4-oxopyridyl]-2-ethanesulfonic acid and I-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-oxopyridine were given by gavage at I .79 mniol/kg. A control group received similar volumes of distilled water. An additional group of rats received a subcutaneous injection of desferrioxamine at 1.79 mniol/ kg. Urine samples were collected daily for three consecutive days and the animals were killed after this period. Samples of brain, bone, liver. kidney and spleen were collected. Although desferrioxamine, 1,2-dimethyl-3-hydroxypirid-4-one. I -@-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, I-@-methoxybenzyl)-2-niethyl-3-hydroxypyrid-4-one. I-@-methylbenryl)-2-ethyl-3-hydroxypyrid-4-one, I-[3-hydroxy-2-niethyl-4-oxopyridyl]-2-ethanesulfonic acid and I-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-oxopyridine significantly enhanced the total excretion of A1 into urine, only treatment with 1 -@-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one and l-benzyl-2-elhyl-3-hydroxypyrid-4-one significantly reduced Al concentrations in all analyzed tissues. No beneficial effects of the remaining chelators on A1 mobilization were observed. Further studies on the effects of some 3-hydoxrypyrid-4-ones on A1 removal can be of interest for the treatment of A1 accumulation and toxicity.

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Aluminum chelation: Chemistry, clinical, and experimental studies and the search for alternatives to desferrioxamine

Cited by 75 publications

References 199 publications

Metal Ion Physiopathology in Neurodegenerative Disorders

Metal Ion Physiopathology in Neurodegenerative Disorders

Transient Proliferation of Proanthocyanidin-Accumulating Cells on the Epidermal Apex Contributes to Highly Aluminum-Resistant Root Elongation in Camphor Tree

Aluminium Distribution and Excretion: A Comparative Study of a Number of Chelating Agents in Rats

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