TY - JOUR T1 - Inhibition of Nitric Oxide Synthesis Enhances Teratogenic Effects Induced by Valproic Acid JF - In Vivo JO - In Vivo SP - 513 LP - 518 VL - 27 IS - 4 AU - GIAN MARIO TIBONI AU - FRANCESCO CHIARELLI AU - ALBERTO VERROTTI Y1 - 2013/07/01 UR - http://iv.iiarjournals.org/content/27/4/513.abstract N2 - Background/aim: The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity. Materials and Methods: On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation. Results: After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%. Conclusion: Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis. ER -