{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:20:40Z","timestamp":1792858840642,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Reproductive Toxicology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.reprotox.2020.08.012","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T23:28:21Z","timestamp":1604446101000},"page":"152-159","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Valproic acid alters nitric oxide status in neurulating mouse embryos"],"prefix":"10.1016","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-5230","authenticated-orcid":false,"given":"Gian Mario","family":"Tiboni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalisa","family":"Ponzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Ferrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Franceschelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Speranza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Patruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.reprotox.2020.08.012_bib0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.reprotox.2009.02.014","article-title":"Valproic acid in pregnancy: how much are we endangering the embryo and fetus?","volume":"28","author":"Ornoy","year":"2009","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0010","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1212\/WNL.0000000000001182","article-title":"Liverpool and Manchester Neurodevelopment Group, IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study","volume":"84","author":"Baker","year":"2015","journal-title":"Neurology"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0015","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.reprotox.2014.04.005","article-title":"Developmental neurotoxicity and anticonvulsant drugs: a possible link","volume":"48","author":"Verrotti","year":"2014","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0020","first-page":"303","article-title":"Teratology of valproic acid: an updated review of the possible mediating mechanisms","volume":"70","author":"Ponzano","year":"2018","journal-title":"Minerva Ginecol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0025","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1097\/01.fpc.0000170914.11898.3a","article-title":"Valproic acid-induced skeletal malformations: associated gene expression cascades","volume":"28","author":"Massa","year":"2005","journal-title":"Pharmacogenet. Genomics"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0030","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/bdrc.20082","article-title":"Inhibition of histone deacetylase as a new mechanism of teratogenesis","volume":"78","author":"Menegola","year":"2006","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0035","first-page":"513","article-title":"Inhibition of nitric oxide synthesis enhances teratogenic effects induced by valproic acid","volume":"27","author":"Tiboni","year":"2013","journal-title":"In Vivo"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0040","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.reprotox.2015.03.004","article-title":"Prevention of valproic acid-induced neural tube defects by sildenafil citrate","volume":"56","author":"Tiboni","year":"2015","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0045","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.mod.2017.12.001","article-title":"Valproic acid disrupts the biomechanics of late spinal neural tube closure in mouse embryos","volume":"149","author":"Hughes","year":"2018","journal-title":"Mech. Dev."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0050","doi-asserted-by":"crossref","first-page":"109264","DOI":"10.1016\/j.mehy.2019.109264","article-title":"M2-like cells from the macrophage lineage might play a central role in closure of the embryonic neural tube","volume":"129","author":"Block","year":"2019","journal-title":"Med. Hypotheses"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0055","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.2174\/1381612043383665","article-title":"Teratological consequences of nitric oxide synthesis inhibition","volume":"10","author":"Tiboni","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0060","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.2174\/1381612820666140205150437","article-title":"Nitric oxide and teratogenesis: an update","volume":"20","author":"Tiboni","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0065","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1021\/jm800846u","article-title":"Synthesis, biological evaluation, and docking studies of N-substituted acetamidines as selective inhibitors of inducible nitric oxide synthase","volume":"52","author":"Maccallini","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0070","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1177\/1352458508088918","article-title":"Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone)","volume":"14","author":"Iarlori","year":"2008","journal-title":"Mult. Scler."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0075","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/j.bbagen.2012.08.014","article-title":"Novel aminobenzyl-acetamidine derivative modulate the differential regulation of NOSs in LPS induced inflammatory response: role of PI3K\/Akt pathway","volume":"1820","author":"Patruno","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0080","doi-asserted-by":"crossref","first-page":"6495","DOI":"10.1016\/j.bmcl.2010.09.059","article-title":"N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase","volume":"20","author":"Maccallini","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0085","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1177\/153537020322800809","article-title":"Effect of chronic hypoxia on inducible nitric oxide synthase expression in rat myocardial tissue","volume":"228","author":"Grilli","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0090","doi-asserted-by":"crossref","first-page":"e12432","DOI":"10.1111\/cpr.12432","article-title":"Extremely low-frequency electromagnetic fields accelerates wound healing modulating MMP-9 and inflammatory cytokines","volume":"51","author":"Patruno","year":"2018","journal-title":"Cell Prolif."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0095","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0891-5849(01)00480-4","article-title":"Redox environment of the cell as viewed through the redox state of the glutathione disulfide\/glutathione couple","volume":"30","author":"Schafer","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0100","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1021\/mp500431r","article-title":"Synthesis of a novel cyclic prodrug of S-allyl-glutathione able to attenuate LPS-induced ROS production through the inhibition of MAPK pathways in U937 cells","volume":"12","author":"Patruno","year":"2015","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0105","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1271\/bbb.66.2732","article-title":"Design of a fluorescent electrophoretic mobility shift assay improved for the quantitative and multiple analysis of protein-DNA complexes","volume":"66","author":"Onizuka","year":"2002","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0110","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"issue":"May-Jun","key":"10.1016\/j.reprotox.2020.08.012_bib0115","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1089\/ars.2006.8.949","article-title":"Cross-talk between constitutive and inducible NO synthase: an update","volume":"8","author":"Persichini","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0120","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/bdrb.20100","article-title":"Production of axial skeletal malformations with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the mouse","volume":"80","author":"Tiboni","year":"2007","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0125","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/tera.1420490605","article-title":"Dysmorphogenic effects of nitric oxide (NO) and NO-synthase inhibition: studies with intra-amniotic injections of sodium nitroprusside and N(G)-monomethyl-L-arginine","volume":"49","author":"Lee","year":"1994","journal-title":"Teratology"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0130","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1124\/pr.110.002907","article-title":"cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action","volume":"62","author":"Francis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0135","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/tera.1066","article-title":"Transplacental exposure to methylene blue initiates teratogenesis in the mouse: preliminary evidence for a mechanistic implication of cyclic GMP pathway disruption","volume":"64","author":"Tiboni","year":"2001","journal-title":"Teratology"},{"key":"10.1016\/j.reprotox.2020.08.012_bib0140","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/dvdy.10164","article-title":"Evidence that nitric oxide regulates cell-cycle progression in the developing chick neuroepithelium","volume":"225","author":"Traister","year":"2002","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0145","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0014-4827(03)00215-5","article-title":"Nitric oxide is involved in establishing the balance between cell cycle progression and cell death in the developing neural tube","volume":"288","author":"Plachta","year":"2003","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0150","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1471-4159.2005.03542.x","article-title":"Neural tube closure depends on nitric oxide synthase activity","volume":"96","author":"Nachmany","year":"2006","journal-title":"J. Neurochem."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0155","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/bdra.20386","article-title":"Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis","volume":"79","author":"Alexander","year":"2007","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0160","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/0002-9378(94)90141-4","article-title":"Nitric oxide inhibition causes intrauterine growth retardation and hind-limb disruption in rats","volume":"171","author":"Diket","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0165","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0890-6238(97)00033-6","article-title":"The teratogenicity of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor in rats","volume":"11","author":"Fantel","year":"1997","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0170","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1203\/01.PDR.0000069840.78984.76","article-title":"The nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) causes limb defects in mouse fetuses: protective effect of acute hyperoxia","volume":"54","author":"Tiboni","year":"2003","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0175","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/01.RES.0000037983.07158.B1","article-title":"Inhibitors of histone deacetylation down regulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis","volume":"91","author":"R\u00f6ssig","year":"2002","journal-title":"Circ. Res."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0180","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1096\/fasebj.11.2.9039953","article-title":"An essential role for free radicals and derived species in signal transduction","volume":"11","author":"Lander","year":"1997","journal-title":"FASEB J."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0185","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nrm1569","article-title":"Protein S-nitrosylation: purview and parameters","volume":"6","author":"Hess","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0190","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0165-6147(00)01499-1","article-title":"The dual personality of NO","volume":"21","author":"Colasanti","year":"2000","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0195","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1161\/01.ATV.18.11.1796","article-title":"NO inhibits cytokine-induced iNOS expression and NF-kappaB activation by interfering with phosphorylation and degradation of IkappaB-alpha","volume":"18","author":"Katsuyama","year":"1998","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0200","doi-asserted-by":"crossref","first-page":"14214","DOI":"10.1074\/jbc.270.23.14214","article-title":"Induction and stabilization of IkBa by nitric oxide mediates inhibition of NF-kB","volume":"270","author":"Peng","year":"1995","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.reprotox.2020.08.012_bib0205","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.279.5351.673","article-title":"Lipid-regulated kinases: some common themes at last","volume":"279","author":"Downward","year":"1998","journal-title":"Science"}],"container-title":["Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S089062382030201X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S089062382030201X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:54:43Z","timestamp":1760190883000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S089062382030201X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":41,"alternative-id":["S089062382030201X"],"URL":"https:\/\/doi.org\/10.1016\/j.reprotox.2020.08.012","relation":{},"ISSN":["0890-6238"],"issn-type":[{"value":"0890-6238","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Valproic acid alters nitric oxide status in neurulating mouse embryos","name":"articletitle","label":"Article Title"},{"value":"Reproductive Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.reprotox.2020.08.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}