Valproic Acid Downregulates RBP4 and Elicits Hypervitaminosis A-Teratogenesis—A Kinetic Analysis on Retinol/Retinoic Acid Homeostatic System

摘要: Background Valproic acid (VPA) is an antiepileptic and anti-migraine prophylactic drug. VPA exhibits two severe side effects, namely acute liver toxicity teratogenicity. These effects are usually seen at the genetic somatic levels. The cited action mechanisms involve inhibition of histone deacetylase, hypofolatenemia, hyperhomocysteinemia, reactive oxidative stress. proteomic information associated with teratogenicity still unavailable. We hypothesized that analysis might help us identify functional proteins could be relevantly affected by VPA, this phenomenon very sensitive in early embryonic stage, resulting teratogenicity. Methodology/Principal Findings Proteomic on chicken embryos Hamburger Hamilton (HH) stage 28 showed there were significant downregulations ovotransferrins, carbonic anhydrase-2, retinol binding protein-4 (RBP4), NADH cytochrome b5 reductase 2 (CYB5R2), apolipoprotein A1, protein SET, together upregulation 60S ribosomal L22. Among these, RBP4 was most significantly downregulated (−32%). Kinetic suggested situation trigger hypervitaminosis A (+39.3%), a condition has been well known to induce teratogenesis.. Conclusions/Significance This first report showing dowregulates RBP4. Our finding not only led possible mechanism teratogenesis, but also initiated new preventive strategies for avoiding teratogeneis.