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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
1995-8-3
|
| pubmed:abstractText |
Chronic administration of amiodarone (AMIO), widely used by clinicians for the treatment of therapy-resistant cardiac arrhythmias, is frequently associated with serious side-effects. AMIO and its main metabolite desethylamiodarone (DEA) are known to induce phospholipidosis in vivo and in cultured cells presumably by inhibition of lysosomal phospholipid degradation. D-alpha-Tocopherol = vitamin E (alpha-TOC) was able to reduce AMIO and DEA toxicity in cell cultures. Results from the present study showed that alpha-TOC reduced phospholipidosis in cultured human skin fibroblasts chronically exposed to micromolar concentrations of AMIO and DEA and inhibited cumulative uptake of the drugs in a dose-dependent manner. A linear correlation was observed between cellular AMIO levels and phospholipid accumulation suggesting a stoichiometric relationship. alpha-TOC was also effective in clearing previously accumulated phospholipids after discontinuation of the drug treatment. The results can best be explained by an interference of alpha-TOC (a) with drug-phospholipid complex formation responsible for both phospholipid storage and drug accumulation, and (b) with pre-existing drug-phospholipid complexes, accelerating their dissociation and rendering phospholipids to substrates for lysosomal phospholipases. The finding raises hope that side-effects of AMIO and DEA can be prevented or made reversible by the administration of alpha-TOC. It must, however, be proven that the antiarrhythmic drug will still be effective.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0006-2952
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
16
|
| pubmed:volume |
49
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1741-5
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading | |
| pubmed:year |
1995
|
| pubmed:articleTitle |
Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells.
|
| pubmed:affiliation |
Department of Pharmacology, University of Bern, Switzerland.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|