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 journalArticle

10 Citations (Scopus)

Abstract

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
Volume41
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Valproic Acid
Vitamin E
Embryonic Structures
Chickens
S-Adenosylhomocysteine
Muscles
Neural Tube Defects
Carnitine
Zygote
Homocysteine
Chick Embryo
Malondialdehyde
Glutathione
resveratrol
Interleukin-6
Reactive Oxygen Species
Triglycerides
Up-Regulation
Down-Regulation
Control Groups

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Resveratrol and vitamin E rescue valproic acid-induced teratogenicity : The mechanism of action. / Hsieh, Chiu Lan; Chen, Kuan Chou; Lin, Ping Xiao; Peng, Chiung Chi; Peng, Robert Y.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 41, No. 3, 2014, p. 210-219.

Research output: Contribution to journalArticle

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abstract = "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.",
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