Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4 Pt 1
pubmed:dateCreated
1992-11-13
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0106-9543
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
183-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Intracellular distribution and effect of the antimalarial drug mefloquine on lysosomes of rat liver.
pubmed:affiliation
Department of Pathology, Huddinge University Hospital, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't