Document Detail


Comparative teratogenicity and metabolism of all-trans retinoic acid, all-trans retinoyl beta-glucose, and all-trans retinoyl beta-glucuronide in pregnant Sprague-Dawley rats.
MedLine Citation:
PMID:  8475455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
When single large equimolar doses (0.38-0.41 mmol/kg BW) of all-trans retinoic acid (RA), all-trans retinoyl beta-glucose (RBGL), and all-trans retinoyl beta-glucuronide (RBG) are administered orally in oil on day 8.5 of pregnancy to Sprague-Dawley rats, RA and RBGL proved highly teratogenic, whereas RBG was not. Indeed, fetuses from RBG-treated dams were 16% heavier (P < 0.01) than control fetuses. After dosing with RA and RBGL, RA appeared in large amounts within 0.5 h in the maternal plasma and within 1.0 h in the embryo. In contrast, orally administered RBG seemed to be absorbed much more slowly, to be converted very slowly to RA, and not to accumulate either as RBG or as RA in the embryo. When incubated in vitro with embryos and attached membranes, however, both all-trans RBG and all-trans RA were partially converted to 13-cis RA. The nonteratogenicity of RBG, in contrast to RA, seems to be due to a much slower rate of GI absorption, a slow rate of hydrolysis to RA, a limited passage from the maternal circulation into the embryo, and a lower inherent toxicity.
Authors:
D B Gunning; A B Barua; J A Olson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Teratology     Volume:  47     ISSN:  0040-3709     ISO Abbreviation:  Teratology     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-05-20     Completed Date:  1993-05-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0153257     Medline TA:  Teratology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  29-36     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced*
Animals
Female
Fetus / metabolism
Glucose / analogs & derivatives*,  chemistry,  metabolism,  toxicity
Liver / metabolism
Maternal-Fetal Exchange
Pregnancy
Rats
Rats, Sprague-Dawley
Stereoisomerism
Structure-Activity Relationship
Tretinoin / analogs & derivatives*,  chemistry,  metabolism,  toxicity*
Grant Support
ID/Acronym/Agency:
DK 39733/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/retinoylglucose; 302-79-4/Tretinoin; 401-10-5/retinoyl glucuronide; 50-99-7/Glucose

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


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