title: Simultaneous folate intake may prevent adverse effect of valproic acid on neurulating nervous system.
abstract: OBJECTIVE
  The aim of this study is to elucidate the preventive effect of folic acid (FA) on teratogenic effects of valporic acid (VA) in early stage chick embryos on neural tube development.
  
  
  METHODS
  One hundred and fifty specific pathogen-free (SPF) chick eggs were used to investigate the neurulation in five groups. Group A was the control group. Group B was injected 0.02 ml of saline (0.9% NaCl) and was used for sham group. VA (0.72 mg) in 0.02 ml saline was injected in Group C, and 0.342 mcg of FA in 0.02 ml NaCl were administered to the embryos in Group D. VA (0.72 mg) + 0.342 mcg of FA in 0.02 ml saline were administered simultaneously to the eggs in Group E. At the end of 72 h, all embryos were extracted from eggs and were fixed, and for histological analyses hematoxylin and eosine was used, for detection of apoptotic cells terminal deoxyribonucleotide transferase-mediated dUTP-X nick end labeling (TUNEL) was used and for distribution of P53, bcl-2 and caspase-3, caspase-6, caspase-8 and caspase-9 immunoperoxidase techniques were used.
  
  
  RESULTS
  While there were no neural tube defects in the embryos of groups A, B and D, eight embryos died in group C and there were 12 embryos with retarded embryological development. In contrast to that, no death was observed in group E, but only eight embryos were detected with maldevelopmental delay stage.
  
  
  CONCLUSIONS
  These results suggested that VA may induce apoptotic mechanisms but not through the p53 pathway. In addition, FA effectively prevents the teratogenic influence of VA on chick embryo at neurulation stages by stopping cascade of apoptosis before caspase 3 expression.
authors.affiliation: Faculty of Medicine, Department of Neurosurgery, Celal Bayar University, Manisa, Turkey. umuras@yahoo.com
authors.forename: Ahmet Sukru
authors.initials: AS
authors.lastname: Umur
authors.forename: Mehmet
authors.initials: M
authors.lastname: Selcuki
authors.forename: Adem
authors.initials: A
authors.lastname: Bursali
authors.forename: Nurcan
authors.initials: N
authors.lastname: Umur
authors.forename: Burcu
authors.initials: B
authors.lastname: Kara
authors.forename: H Seda
authors.initials: HS
authors.lastname: Vatansever
authors.forename: Yusuf Kurtulus
authors.initials: YK
authors.lastname: Duransoy
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000633:toxicity; D002642:Chick Embryo; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D005492:Folic Acid / Q000008:administration & dosage*; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology*; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control; D054261:Neurulation / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D005492:Folic Acid