Document Detail


Effect of co-administration of retinoids on rat embryo development in vitro.
MedLine Citation:
PMID:  12962289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Excess retinyl palmitate (vitamin A) induces a variety of malformations in many mammalian species, yet retinyl palmitate is not thought to be the proximate teratogen. Many metabolites are generated after oral dosing several of which are, individually teratogenic. It is not known whether these metabolites when present simultaneously interact in an additive or synergistic manner. METHODS: Whole rat embryos were cultured with retinol, all-trans retinoic acid (tRA), 4-oxo all-trans retinoic acid (4otRA) or 9-cis retinoic acid (9cRA). Retinoids were added singly or in paired combinations at the start of culture and embryos were examined for evidence of dysmorphogenesis at the end of culture. Retinoids were added at both subthreshold and supra-threshold concentrations. RESULTS: Co-administration of subthreshold concentrations of tRA and 4otRA, retinol and tRA or 4otRA and 4otRA and 9cRA resulted in a greater frequency of abnormal embryos compared to single administration of each retinoid. CONCLUSIONS: Knowledge of the way in which retinyl palmitate metabolites interact should refine our ability to predict risk from a potentially teratogenic event e.g., accidental overdose with RP during human pregnancy.
Authors:
Helen E Ritchie; Patricia D Brown-Woodman; Ann Korabelnikoff
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  67     ISSN:  1542-0752     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-09-09     Completed Date:  2004-02-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  444-51     Citation Subset:  IM    
Affiliation:
School of Biomedical Sciences, University of Sydney, Cumberland Campus, Lidcombe, NSW, Australia.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced*
Animals
Dose-Response Relationship, Drug
Drug Combinations
Embryo, Mammalian / drug effects*
Female
Organ Culture Techniques
Pregnancy
Rats
Rats, Sprague-Dawley
Retinoids / toxicity*
Teratogens / toxicity*
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Retinoids; 0/Teratogens

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


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