Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)‐dependent, reactive oxygen species (ROS)‐mediated mechanism

ABSTRACT Thalidomide (TD) causes birth defects in humans and rabbits via several potential mechanisms, including bioactivation by embryonic prostaglandin H synthase (PHS) enzymes to a reactive intermediate that enhances reactive oxygen species (ROS) formation. We show herein that TD in rabbit embryo...

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Bibliographic Details
Published in:The FASEB journal 2011-07, Vol.25 (7), p.2468-2483
Main Authors: Lee, Crystal J. J., Gonçalves, Luisa L., Wells, Peter G.
Format: Article
Language:English
Subjects:
2‐phthalimidoglutaramic acid
2‐phthalimidoglutaric acid
5,8,11,14-Eicosatetraynoic Acid - pharmacology
8‐oxoguanine
Animals
Aspirin - pharmacology
Brain - abnormalities
Brain - drug effects
Brain - metabolism
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - metabolism
Embryo, Mammalian - abnormalities
Embryo, Mammalian - drug effects
Embryo, Mammalian - metabolism
Female
Hydrolysis
Limb Buds - abnormalities
Limb Buds - drug effects
Limb Buds - metabolism
Male
Molecular Structure
otic vesicle development
Oxidation-Reduction - drug effects
Prostaglandin-Endoperoxide Synthases - metabolism
Rabbits
Reactive Oxygen Species - metabolism
Teratogens - chemistry
Teratogens - metabolism
Teratogens - toxicity
Thalidomide - chemistry
Thalidomide - metabolism
Thalidomide - toxicity
Tissue Culture Techniques
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Summary:ABSTRACT Thalidomide (TD) causes birth defects in humans and rabbits via several potential mechanisms, including bioactivation by embryonic prostaglandin H synthase (PHS) enzymes to a reactive intermediate that enhances reactive oxygen species (ROS) formation. We show herein that TD in rabbit embryo culture produces relevant embryopathies, including decreases in head/brain development by 28% and limb bud growth by 71% (P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.10-178814