| Evaluation of the rat embryo culture system as a predictive test for human teratogens. | |
| | |
MedLine Citation:
|
PMID: 8012899 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Ingestion of the anticonvulsant drug valproic acid and of the angiotensin converting enzyme inhibitor captopril during pregnancy has been associated with abnormal fetal outcome in humans. In contrast, the use of the antiinflammatory drug ibuprofen and the antihistamine diphenhydramine has not been documented to be embryotoxic in humans. We evaluated the rat embryo culture system as a predictive model of teratogenesis, using these four drugs as test agents. Valproic acid, ibuprofen, and diphenhydramine were embryotoxic, inducing concentration-dependent decreases in growth and a significant increase in anomalies. Valproic acid caused an increase in neural tube defects, ibuprofen increased the incidence of abnormal maxillary processes, and diphenhydramine increased the number of embryos with distorted body morphology. These abnormalities were induced at concentrations of valproic acid and diphenhydramine that are used clinically, but ibuprofen only induced toxicity at concentrations greatly exceeding the therapeutic range. Captopril was not embryotoxic up to 5 mM, the highest concentration tested. These results suggest that the rat embryo culture system produces both false positive and false negative data on the teratogenic potential of drugs. Although such an in vitro assay may be suitable to determine the mechanism of teratogenesis, it is not a sensitive indicator of potential human teratogens on its own. These data support the view that in vitro systems can only supplement clinical and epidemiological observations in humans, possibly as a method to determine mechanisms of actions of teratogens. |
| | |
Authors:
|
I Guest; H S Buttar; S Smith; D R Varma |
Related Documents
:
|
12141409 - Epsilon-aminocaproic acid and renal complications: case report and review of the litera... 605089 - The effect of caproic acid, handling technique and storage times on the fertility of fo... 23140499 - Diversity of phenolic profiles in the fruit skin of prunus domestica plums and related ... 20863429 - Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or... 11897429 - Carbapenem antibiotics inhibit valproic acid transport in caco-2 cell monolayers. 11716839 - Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic v... 16259119 - Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluatio... 12831199 - Capillary electrochromatography of peptides on microfabricated poly(dimethylsiloxane) c... 22938939 - A meta-analytic review of polyunsaturated fatty acid compositions in dementia. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Canadian journal of physiology and pharmacology Volume: 72 ISSN: 0008-4212 ISO Abbreviation: Can. J. Physiol. Pharmacol. Publication Date: 1994 Jan |
Date Detail:
|
Created Date: 1994-07-26 Completed Date: 1994-07-26 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0372712 Medline TA: Can J Physiol Pharmacol Country: CANADA |
Other Details:
|
Languages: eng Pagination: 57-62 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology and Therapeutics, McGill University, Montréal, PQ, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abnormalities, Drug-Induced
/
pathology Animals Captopril / toxicity DNA / metabolism Diphenhydramine / toxicity Embryo, Mammalian / drug effects* False Negative Reactions False Positive Reactions Female Humans Ibuprofen / toxicity Neural Tube Defects / chemically induced Organ Culture Techniques Pregnancy Rats Teratogens / toxicity* Valproic Acid / toxicity |
| Chemical | |
Reg. No./Substance:
|
0/Teratogens; 15687-27-1/Ibuprofen; 58-73-1/Diphenhydramine; 62571-86-2/Captopril; 9007-49-2/DNA; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibition of mouse embryonic, yolk sac, and limb-bud functions by the methyl isocyanate metabolite ...
Next Document: Myocardial energetics and blood flow in acute rapid ventricular pacing.