Linked Life Data

9144452

Source:http://linkedlifedata.com/resource/pubmed/id/9144452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-6-2
pubmed:abstractText
A subpopulation of CF-1 mice is unusual in its sensitivity to the avermectins, abamectin and ivermectin, with neurotoxicity occurring at 100-fold lower doses than in other species and mouse strains. We have shown that the sensitive CF-1 mice are deficient in P-glycoprotein in the intestinal epithelium and brain capillary endothelium, tissues forming the principle barriers for penetration into the systemic circulation and central nervous system, respectively. Consistent with the role of P-glycoprotein as a barrier to tissue entry, the plasma and tissue levels of radiolabeled ivermectin in the sensitive mice were markedly higher than in the insensitive mice, particularly in brain, the target organ for toxicity. Insensitive CF-1 and CD-1 mice showed abundant levels of P-glycoprotein in these tissues and tolerated doses of abamectin at least 50-fold the minimum toxic dose in the sensitive subgroup. In view of these findings in CF-1 mice with both abamectin and the structural analog ivermectin, which is used extensively in the treatment of human filariasis with no evidence of neurotoxicity, it is likely that this protein, found in human brain endothelium, is highly conserved in the human population.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
357-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
P-glycoprotein deficiency in a subpopulation of CF-1 mice enhances avermectin-induced neurotoxicity.
pubmed:affiliation
Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
pubmed:publicationType
Journal Article, Comparative Study