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Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Identifieur interne : 002B30 ( Main/Exploration ); précédent : 002B29; suivant : 002B31

Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Auteurs : Ulrich E. Honegger [Suisse] ; Isabel Scuntaro [Suisse] ; Ulrich N. Wiesmann [Suisse]

Source :

Biochemical Pharmacology [ 0006-2952 ] ; 1995.

RBID : ISTEX:E5848D3B5A218452FAB9A5805DA9C9B4E1EA00DA

English descriptors

Abstract

Abstract: 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-α-Tocopherol = vitamin E (α-TOC) was able to reduce AMIO and DEA toxicity in cell cultures. Results from the present study showed that α-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. α-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 α-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 α-TOC. It must, however, be proven that the antiarrhythmic drug will still be effective.

Url:

https://api.istex.fr/ark:/67375/6H6-R5DDNP0B-L/fulltext.pdf

DOI: 10.1016/0006-2952(95)00100-E

Affiliations:

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Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMIO, amiodarone (2-butyl-3-(3′-5′-diiodo-4′α-diethylaminoethoxybenzoyl)benzofuran)</term>
<term>DEA, desethylamiodarone</term>
<term>MEM, Eagle's minimal essential medium</term>
<term>PL, phospholipid</term>
<term>amiodarone</term>
<term>desethylamiodarone</term>
<term>fibroblast cultures</term>
<term>lysosomes</term>
<term>phospholipidosis</term>
<term>α-TOC, D-α-tocopherol = vitamin E</term>
<term>α-tocopherol</term>
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<keywords scheme="Teeft" xml:lang="en"><term>Alveolar macrophages</term>
<term>Amio</term>
<term>Amiodarone</term>
<term>Amiodarone toxicity</term>
<term>Butylated hydroxytoluene</term>
<term>Cell cultures</term>
<term>Cellular</term>
<term>Cellular accumulation</term>
<term>Cellular protein</term>
<term>Cellular uptake</term>
<term>Chronic exposure</term>
<term>Confluent fibroblast cultures</term>
<term>Confluent skin fibroblast cultures</term>
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<term>Culture media</term>
<term>Culture medium</term>
<term>Cultured</term>
<term>Cultured cells</term>
<term>Cumulative uptake</term>
<term>Desethylamiodarone</term>
<term>Drug accumulation</term>
<term>Drug doses</term>
<term>Drug exposure</term>
<term>Drug uptake</term>
<term>Fibroblast</term>
<term>Foetal calf serum</term>
<term>Free drug</term>
<term>Glass petri dishes</term>
<term>Linear correlation</term>
<term>Lysosomal</term>
<term>Lysosomal phospholipases</term>
<term>Membrane fluidity</term>
<term>Micromolar concentrations</term>
<term>Phospholipid</term>
<term>Phospholipidosis</term>
<term>Recovery period</term>
<term>Skin fibroblasts</term>
<term>Toxicity</term>
<term>Untreated control cells</term>
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<front><div type="abstract" xml:lang="en">Abstract: 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-α-Tocopherol = vitamin E (α-TOC) was able to reduce AMIO and DEA toxicity in cell cultures. Results from the present study showed that α-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. α-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 α-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 α-TOC. It must, however, be proven that the antiarrhythmic drug will still be effective.</div>
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Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Source :

English descriptors

Abstract

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Pour mettre un lien sur cette page dans le réseau Wicri