Resveratrol and vitamin E rescue valproic acid-induced teratogenicity: The mechanism of action

Chiu Lan Hsieh, Kuan Chou Chen, Ping Xiao Lin, Chiung Chi Peng, Robert Y. Peng

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Valproic acid (VPA) induces haemorrhagic liposis of the cervical muscles in the chicken embryo model (CEM). Vitamin E and resveratrol (RV) exhibit prominent anti-oxidative and glutathione (GSH)-protecting effects. In the present study we hypothesized that vitamin E and RV would ameliorate VPA induced haemorrhagic liposis in chick embryos. To this end, 120 Day 0 fertilized eggs were divided into 10 groups (n = 12 in each). The effects of different combinations of VPA (60 mmol/L), RV (0.2 and 2.0 mmol/L) and vitamin E (0.2 and 2.0 mmol/L) applied to Hamburger and Hamilton (HH) Stage 10 (Day 1.5) embryos were tested in the CEM using established methods. Both RV and vitamin E (both at 2.0 mmol/L) effectively rescued neural tube defects in the early stage CEM and inhibited the malformation rate compared with that in the control group (8.4% and 5.0% vs 36.5 ± 3.0%, respectively; P <0.05) and suppressed serum homocysteine and S-adenosylhomocysteine concentrations, downregulated cervical muscular carnitine, triglycerides, H2O2, malondialdehyde, interleukin-6 and ACC expression (P <0.05 for all) and upregulated CPT1 expression and GSH (P <0.05 for both). The haemorrhagic liposis of cervical muscles can be alleviated by RV and vitamin E. It appears that the main mechanism of action of RV and vitamin E in rescuing VPA-induced teratogenicity is through the suppression of reactive oxygen species and upregulation of GSH.

Original languageEnglish
Pages (from-to)210-219
Number of pages10
JournalClinical and Experimental Pharmacology and Physiology
Issue number3
Publication statusPublished - Mar 2014


  • ACC
  • CPT1
  • Chicken embryo model
  • Haemorrhagic liposis
  • Resveratrol
  • Valproic acid
  • Vitamin E

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Pharmacology


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