title: Prevention of valproic acid-induced neural tube defects by sildenafil citrate.
abstract: This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis.
authors: Dipartimento di Medicina e Scienze dell'Invecchiamento, Università "G. d'Annunzio" Chieti-Pescara, Italy. Electronic address: tiboni@unich.it.
authors: Gian Mario
authors: GM
authors: Tiboni
authors: Dipartimento di Medicina e Scienze dell'Invecchiamento, Università "G. d'Annunzio" Chieti-Pescara, Italy.
authors: Adalisa
authors: A
authors: Ponzano
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000175:diagnosis / Q000517:prevention & control*; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D014635:Valproic Acid
chemical_list: D018696:Neuroprotective Agents; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D014635:Valproic Acid; D000068677:Sildenafil Citrate
keywords: Axial skeletal defects; Neural tube defects; Nitric oxide; Sildenafil citrate; Teratogenicity; Valproic acid