The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in 
genetic and somatic levels, causing teratogenesis involving neurotubular defects 
(NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to 
spina bifida aperta. A diversity of nutraceutics have been tried to alleviate 
the risk of VPA-teratogenicity. The effect was varying. In order to promote the 
preventive prescription, to find out its action mechanism can be rather crucial. 
We used chicken embryo model to try the effect of folic acid (FA), ascorbic acid 
(AA), and N-acetyl cysteine (NAC). VPA at 30mM showed the higher malformation 
rate (66.7%) with the least mortality (22.2%). Pathological findings indicated 
that the cervical muscle was more susceptible to VPA injury than the ankle 
muscle. VPA downregulated levels of superoxide dismutase (SOD), glutathione 
(GSH), histone deacetylase (HDAC) and folate, and upregulated H(2)O(2) and 
homocysteine. FA, AA, and NAC significantly upregulated SOD, but only AA alone 
activated GSH. AA and NAC downregulated H(2)O(2), while FA was totally 
ineffective. All three nutraceutics comparably rescued HDAC with simultaneously 
suppressed homocysteine accumulation and folate re-elevation, although less 
effectively by NAC. Based on these data, we conclude VPA possesses "Multiple 
Point Action Mechanism". In addition to affecting the cited transcription and 
translation levels, we hypothesize that VPA competitively antagonize the 
glutamic acid to couple with pteroic acid in biosynthesis of dihydrofolic acid 
(DHFA). H(2)O(2) directly destroyed the NADPH reducing system at dihydrofolate 
reductase (DHFR) and methylene tetrahydrofolate reductase (MTHFR) levels, while 
completely restored by AA, an implication in preservation of intact apoenzymes. 
In addition, the GSH-GSSG system is sandwiched between the reducing systems 
NADPH/NADP and DHA-AA, its net balance is highly dependent on in situ in vivo 
Redox state, hence folic acid transformation is varying. To rescue the 
VPA-induced teratogenicity, simultaneous multiple prescriptions are suggested.