Document Detail


Aluminum chelation: chemistry, clinical, and experimental studies and the search for alternatives to desferrioxamine.
MedLine Citation:
PMID:  8301696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This review focuses on aluminum (Al) chelation, its chemistry and biology. The toxicology and biology of Al in mammalian organisms are briefly reviewed to introduce the problems associated with excessive Al exposure and accumulation and the challenges facing an effective Al chelator. The basics of Al chelation chemistry are considered to help the reader understand the Al chelation chemical literature. The chemical properties of Al enable prediction of effective functional groups for Al chelation. A compilation of distribution coefficients between octanol and aqueous phases (Do/a) for chelators and their complexes with Al shows the effect of complexation on lipophilicity. A compilation of stability constants for Al.chelator complexes illustrates the role of oxygen in ligands that form stable complexes. The history of clinical Al chelation therapy is reviewed, with emphasis on desferrioxamine (DFO), which has been extensively used since 1980. The beneficial and adverse effects and limitations of DFO use in end-stage renal-diseased patients, in patients with neurodegenerative disorders, including Alzheimer's disease, and in animal models of Al intoxication are presented. The methods to evaluate potential Al chelators in vitro, in vivo, and using computer modeling are discussed. The Al chelation literature is reviewed by the chemical class of chelators, including fluoride, carboxylic acids, amino acids, catechols, polyamino carboxylic acids, phenyl carboxylic acids, the hydroxypyridinones, and hydroxamic acids.
Authors:
R A Yokel
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Journal of toxicology and environmental health     Volume:  41     ISSN:  0098-4108     ISO Abbreviation:  J Toxicol Environ Health     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-03-10     Completed Date:  1994-03-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7513622     Medline TA:  J Toxicol Environ Health     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  131-74     Citation Subset:  IM    
Affiliation:
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aluminum* / adverse effects,  chemistry,  metabolism
Animals
Carboxylic Acids / metabolism
Chelating Agents / adverse effects,  metabolism*,  therapeutic use
Chelation Therapy*
Child
Deferoxamine / adverse effects,  metabolism*,  therapeutic use
Fluorides / metabolism
Humans
Kidney Failure, Chronic / therapy*
Nervous System Diseases / therapy
Rabbits
Rats
Renal Replacement Therapy
Grant Support
ID/Acronym/Agency:
ES K04 174/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Carboxylic Acids; 0/Chelating Agents; 0/Fluorides; 70-51-9/Deferoxamine; 7429-90-5/Aluminum

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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