Abstract
Endogenous and xenobiotic-enhanced oxidative stress may initiate embryonic death and birth defects via reactive oxygen species (ROS) signaling pathways involving nuclear transcription factor-κB (NF-κB). Using embryo culture and a transgenic mouse engineered with a NF-κB–dependent β-galactosidase reporter gene, we employed NF-κB antisense oligonucleotide therapy to determine whether NF-κB signaling contributes to the embryopathic effects of the ROS-initiating teratogen phenytoin. Phenytoin selectively increased NF-κB activity in target tissues and caused embryopathies, both of which were blocked by NF-κB antisense oligonucleotides but not by sense and nonsense oligonucleotide controls. NF-κB signaling may therefore contribute to the mechanism of ROS-mediated embryopathies.
- Received February 24, 2004.
- Accepted June 8, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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