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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 1
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pubmed:dateCreated |
1992-11-13
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pubmed:abstractText |
Mefloquine was administered in a single dose (1-30 mg/100 g) to rats in order to study its subcellular distribution and effects on rat liver lysosomal structure and function. Subcellular fractionation showed a significant enrichment of mefloquine in lysosomes. Even repeated administration of mefloquine did not affect the levels of cytochrome-P-450 or its reductase, indicating, although not proving, that it is not metabolized by this mono-oxygenase system. Mefloquine caused an expansion of the lysosomal apparatus, earliest seen by 24 h and lasting for some 7 days. Initially, cytoplasmic constituents were seen inside the lysosomes. Later, the lysosomes harboured myelin-like figures (multilamellar bodies) disappearing after 7-10 days. The proteolytic and lipolytic capacity was assessed in isolated lysosomes. Mefloquine caused increased protein degradation but decreased breakdown of lipids. Concomitantly, all five major phospholipids (phosphatidyl-choline, -ethanolamine, -inositol, -serine and sphingomyelin) increased in the lysosomes. It is concluded that: (1) mefloquine is a lysosomotropic drug that accumulates in lysosomes; (2) mefloquine impairs lipid degradation with ensuing accumulation of lipids in lysosomes; and (3) lysosomal trapping explains the high volume distribution of mefloquine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0106-9543
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
183-90
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1406082-Animals,
pubmed-meshheading:1406082-Cytochrome P-450 Enzyme System,
pubmed-meshheading:1406082-Lipid Metabolism,
pubmed-meshheading:1406082-Liver,
pubmed-meshheading:1406082-Lysosomes,
pubmed-meshheading:1406082-Male,
pubmed-meshheading:1406082-Mefloquine,
pubmed-meshheading:1406082-Microscopy, Electron,
pubmed-meshheading:1406082-Rats,
pubmed-meshheading:1406082-Rats, Sprague-Dawley
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pubmed:year |
1992
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pubmed:articleTitle |
Intracellular distribution and effect of the antimalarial drug mefloquine on lysosomes of rat liver.
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pubmed:affiliation |
Department of Pathology, Huddinge University Hospital, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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