Linked Life Data

10637134

Source:http://linkedlifedata.com/resource/pubmed/id/10637134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-3-2
pubmed:abstractText
Ethambutol is an efficacious antituberculosis agent. However, its use has been limited by the occurrence of ocular toxicity. To investigate characteristics and possible mechanisms of ethambutol ocular toxicity, we used primary rat retinal cultures as a model. Primary rat retinal cultures were obtained from newborn Sprague-Dawley rats and used for experiments after maturation (DIV > or = 10). Cytopathologic changes were examined under light and electron microscopes. Thy-1 (a membrane glycoprotein expressed by retinal ganglion neurons)-containing neurons and gamma-aminobutyric acid (GABA)-ergic neurons were identified immunocytochemically. Exposure of retinal cultures for 24-48 h to ethambutol induced cytoplasmic vacuolar changes and neuronal loss. Vacuolar changes were partially reversible with the termination of ethambutol exposure. Of neurons, Thy-1(+) ganglion neurons were more vulnerable than GABA(+) neurons. Glutamate antagonists, an antioxidant (trolox), or cycloheximide, did not attenuate either vacuolar changes or neuronal loss. A cell-permeant zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) markedly attenuated vacuolar degeneration and neuronal loss, while the addition of zinc augmented both. In rat retinal cultures, ethambutol induces reversible vacuolar degeneration as well as irreversible neuronal loss, more preferentially of Thy-1(+) ganglion neurons. Contrary to the current theories, ethambutol-induced retinal cytotoxicity in the present study is mediated not by excitotoxicity or zinc deficiency but by a mechanism requiring intracellular zinc. In addition, features of the ethambutol-induced cell death were not consistent with those of apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
107-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc.
pubmed:affiliation
Department of Ophthalmology, University of Ulsan College of Medicine, Seoul, Korea. yhyoon@www.amc.seoul.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't