Resveratrol and vitamin E rescue valproic acid-induced teratogenicity: the mechanism of action.
1. 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. 2. 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. 3. 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, H2 O2 , malondialdehyde, interleukin-6 and ACC expression (P < 0.05 for all) and upregulated CPT1 expression and GSH (P < 0.05 for both). 4. 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.
Graduate Institute of Biotechnology, Changhua University of Education, Changhua, Taiwan.
Chiu-Lan
CL
Hsieh
Kuan-Chou
KC
Chen
Ping-Xiao
PX
Lin
Chiung-Chi
CC
Peng
Robert Y
RY
Peng
D000014:Abnormalities, Drug-Induced / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002642:Chick Embryo; D005978:Glutathione / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D064793:Teratogenesis / Q000187:drug effects*; D014635:Valproic Acid / Q000009:adverse effects*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014810:Vitamin E; D014635:Valproic Acid; D005978:Glutathione; D000077185:Resveratrol
ACC; CPT1; chicken embryo model; haemorrhagic liposis; resveratrol; valproic acid; vitamin E