Prevention and Treatment of Aluminum Toxicity Including Chelation Therapy: Status and Research Needs

Yokel, Robert A.

doi:10.1080/009841096161131

Cited by 54 publications

(1 citation statement)

References 44 publications

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“…Thus, tissue aluminium concentrations in rabbits 1 week after completion of a series of daily i.v. injections for 20 days of aluminium citrate were considerably lower than after the same molar dose of aluminium lactate (Yokel et al, 1996a). However, citrate promotion of aluminium distribution and excretion would only be favoured when the aluminium concentration exceed the Tf metal binding capacity.…”

Section: Modulation Of the Distribution Of Aluminiummentioning

confidence: 83%

Safety of aluminium from dietary intake ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC)

2008

EFS2

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Following a request from the Commission, the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC) was asked to provide a scientific opinion on the safety of aluminium from all sources of dietary intake. In the event the estimated exposure for a particular sub-group(s) is found to exceed the Provisional Tolerable Weekly Intake, a detailed breakdown by exposure source should be provided. Aluminium occurs naturally in the environment and is also released due to anthropogenic activities such as mining and industrial uses, in the production of aluminium metal and other aluminium compounds. A variety of aluminium compounds are produced and used for different purposes, such as in water treatment, papermaking, fire retardant, fillers, food additives, colours and pharmaceuticals. Aluminium metal, mainly in the form of alloys with other metals, has many uses including in consumer appliances, food packaging and cookware. The major route of exposure to aluminium for the general population is through food. Aluminium in drinking water represents another, minor, source of exposure. Additional exposures may arise from the use of aluminium compounds in pharmaceuticals and consumer products. Most unprocessed foods typically contain less than 5 mg aluminium/kg. Higher concentrations (mean levels 5 to 10 mg/kg) were often found in breads, cakes and pastries (with biscuits having the highest levels), some vegetables (with mushrooms, spinach, radish, swiss card, 1 For citation purposes: Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials on a request from European Commission on Safety of aluminium from dietary intake.

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Section: Modulation Of the Distribution Of Aluminiummentioning

confidence: 83%

Safety of aluminium from dietary intake ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC)

2008

EFS2

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Complex formation between aluminium(III) and 2-hydroxy nicotinic acid: an electrospray mass spectrometric investigation

Bertani

Bombi

Bortolini

et al. 1999

Rapid Commun. Mass Spectrom.

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Iron Chelators and Therapeutic Uses

Bergeron

McManis

Weimar

et al. 2003

Burger's Medicinal Chemistry and Drug Discovery

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Iron is an essential cofactor in a variety of biological redox reactions; life without this metal is virtually unknown. Because of its exceptionally poor solubility in the biosphere, bacteria produce relatively low molecular weight, virtually iron(III)‐specific, ligands, siderophores, for the purpose of acquiring this transition metal. On the other hand, higher eukaryotes generate proteins to acquire and store iron. In humans, the process of iron absorption and processing is very tightly controlled. However, the lack of an efficient means of elimination can, under certain conditions, result in iron overload, which can elicit oxidative tissue damage through the Fenton reaction. Accordingly, chelating agents have been tested over the last several decades for the purpose of rendering excess iron excretable. The currently accepted therapy for global iron overload, as occurs after repeated blood transfusions, is a siderophore, desferrioxamine B (DFO), which is administered subcutaneously as its mesylate salt (Desferal). Two synthetic agents, diethylenetriamine pentaacetic acid (DTPA) and 1,2‐dimethyl‐3‐hydroxypyridin‐4‐one (Ferriprox, deferiprone, L1), have been used for the treatment of iron overload as well. Unfortunately, all three of these ligands have drawbacks. The kinetics and lack of oral bioavailability of DFO require that this compound be administered subcutaneously 12 h/day, up to 6 days/week, a regimen with which many patients find it difficult to comply. The lack of chelating specificity of DTPA restricts its use to those who cannot tolerate therapy with DFO; questions remain unanswered regarding the efficacy and toxicity profile of L1. The ongoing efforts to find a worthy successor to DFO include the use of a synthetic agent, N,N ′‐bis(2‐hydroxybenzyl)ethylenediamine‐ N,N ′‐diacetic acid (HBED), which, although it would require subcutaneous administration, is significantly more efficient than DFO. Another avenue is using siderophores (e.g., desferrithiocin, parabactin) as platforms from which to design either orally or parenterally active iron chelators. Because of the necessity of striking a balance between efficacy (i.e., sufficient iron chelation) and toxicity (i.e., excessive iron removal), drug development in the arena of iron chelation therapy presents unique challenges. However, the application of sensible drug design principles predicated on our understanding of iron metabolism, modern synthetic techniques, and the use of appropriate animal models should bring about improved therapeutic agents for the treatment of both global and focal iron overload in the years to come.

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Prevention and Treatment of Aluminum Toxicity Including Chelation Therapy: Status and Research Needs

Cited by 54 publications

References 44 publications

Safety of aluminium from dietary intake ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC)

Safety of aluminium from dietary intake ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC)

Complex formation between aluminium(III) and 2-hydroxy nicotinic acid: an electrospray mass spectrometric investigation

Iron Chelators and Therapeutic Uses

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