Document Detail

Mitochondrial damage revealed by morphometric and semiquantitative analysis of mouse pup cardiomyocytes following in utero and postnatal exposure to zidovudine and lamivudine.
MedLine Citation:
PMID:  15229369     Owner:  NLM     Status:  MEDLINE    
Zidovudine (ZDV), an antiretroviral drug used alone or in combination with other antiretroviral agents to treat HIV-infected pregnant women and their newborn infants, effectively reduces mother-to-child transmission of the virus. That myopathy and cardiomyopathy, related to mitochondrial damage, develop in some adults chronically treated with ZDV has long been known; recently, reports have suggested that similar adverse effects may occur in some infants exposed perinatally. Using a mouse model of human neonatal exposure, we treated pregnant CD-1 mice twice daily with doses of 75 mg/kg ZDV plus 37.5 mg/kg lamivudine throughout gestation and lactation; pups were exposed by direct gavage beginning postnatal day (PND) 4 and sacrificed on PND 28. Hearts were removed rapidly, and ventricles were processed for electron microscopy. Morphometric and semiquantitative morphological analyses were performed on three micrographs from each of three blocks from each of three females and three males from the control and treated groups. Treated mice showed significant increases in the mean area and decreases in the mean number of cardiomyocytic mitochondria compared to controls. We observed clusters of damaged mitochondria more frequently in treated animals than in controls; damage included fragmentation and loss of cristae. These results, demonstrating alterations in cardiomyocytic mitochondria of mice exposed in utero and postnatally, may model cardiac damage reported in human infants similarly exposed to ZDV. Critical insights derived from animal-model data like these may be used to mitigate risks to thousands of human infants receiving essential lifesaving therapy with antiretroviral drugs.
Jack B Bishop; Yoshiro Tani; Kristine Witt; Jo Anne Johnson; Shyamal Peddada; June Dunnick; Abraham Nyska
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Publication Detail:
Type:  Journal Article     Date:  2004-06-30
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  81     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-10     Completed Date:  2005-02-04     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  512-7     Citation Subset:  IM    
Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Animals, Newborn / physiology
Anti-HIV Agents / toxicity*
Lamivudine / toxicity*
Microscopy, Electron
Mitochondria, Heart / pathology*
Myocytes, Cardiac / pathology*
Zidovudine / toxicity*
Reg. No./Substance:
0/Anti-HIV Agents; 134678-17-4/Lamivudine; 30516-87-1/Zidovudine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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