Linked Life Data

8667234

Source:http://linkedlifedata.com/resource/pubmed/id/8667234

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-8-6
pubmed:abstractText
Thalidomide is a teratogenic sedative-hypnotic drug that is structurally similar to phenytoin, which is thought to be bioactivated by prostaglandin H synthase (PHS) and other peroxidases to a teratogenic reactive intermediate. The relevance of this mechanism to thalidomide teratogenicity was evaluated in pregnant New Zealand White rabbits treated with thalidomide at 11:00 A.M. on gestational days 8 to 11, with day 0 indicating the time when sperm were observed in the vaginal fluid. Thalidomide (7.5 mg/kg i.v.) produced mainly fetal limb anomalies analogous to those observed in humans. Thalidomide (25-200 mg/kg i.p.), produced a dose-related increase in a spectrum of fetal anomalies, and in postpartum lethality, but did not produce a reliable incidence of limb anomalies. In subsequent studies, pregnant does received the irreversible PHS inhibitor acetylsalicylic acid (ASA), 75 mg/kg i.p., or its vehicle, followed 2 hr later by thalidomide, 7.5 mg/kg i.v., or its vehicle. ASA pretreatment was remarkably embryoprotective, resulting in respective 61.2 and 61.4% decreases in thalidomide-initiated fetal limb anomalies (P = .002) and postpartum fetal lethality (P < .02), and a small but significant reduction in thalidomide-initiated fetal weight loss. ASA alone did not produce significant embryopathy. These results show that ASA can protect the embryo from thalidomide teratogenicity, suggesting that thalidomide may be bioactivated by PHS to a teratogenic reactive intermediate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1649-58
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Inhibition of thalidomide teratogenicity by acetylsalicylic acid: evidence for prostaglandin H synthase-catalyzed bioactivation of thalidomide to a teratogenic reactive intermediate.
pubmed:affiliation
Faculty of Pharmacy, University of Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't