Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2000-8-15
pubmed:abstractText
3'-azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an approximately 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0889-2229
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
635-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10791874-Animals, pubmed-meshheading:10791874-DNA, Mitochondrial, pubmed-meshheading:10791874-Electron Transport Complex IV, pubmed-meshheading:10791874-Erythrocebus patas, pubmed-meshheading:10791874-Female, pubmed-meshheading:10791874-Fetal Heart, pubmed-meshheading:10791874-Male, pubmed-meshheading:10791874-Microscopy, Electron, pubmed-meshheading:10791874-Mitochondria, pubmed-meshheading:10791874-Mitochondria, Heart, pubmed-meshheading:10791874-Mitochondrial Myopathies, pubmed-meshheading:10791874-Muscle, Skeletal, pubmed-meshheading:10791874-NADH Dehydrogenase, pubmed-meshheading:10791874-Oxidative Phosphorylation, pubmed-meshheading:10791874-Pregnancy, pubmed-meshheading:10791874-Sarcomeres, pubmed-meshheading:10791874-Succinate Dehydrogenase, pubmed-meshheading:10791874-Zidovudine
pubmed:year
2000
pubmed:articleTitle
Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3'-azido-3'-deoxythymidine.
pubmed:affiliation
Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. gerschem@exchange.nih.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.