title: Pharmacology of neural tube defects.
abstract: The pharmacology of neural tube defects (NTDs) is a complex issue. Several theories regarding the etiology of NTDs emphasize the importance of interactions between genetic, environmental, and biochemical factors at a key point in time. One such factor is chronic drug therapy, a potential consequence of which is the formation of toxic drug metabolites, including free radicals (FRs), which have been implicated in the etiology of NTDs. Under normal physiological conditions, FRs are quickly destroyed by antioxidant defense systems. However, FR-mediated cellular damage can occur if these defense systems fail or are overburdened, such as in patients who are genetically deficient in FR scavenging enzyme activity (FRSEA) or who are receiving chronic drug therapy. Congenital defects, including NTDs, resulting from FR-induced damage have been reported in both experimental animals and humans. For example, the use of antiepileptic drugs (AEDs) during pregnancy that have the propensity to form FRs during their metabolism are associated with an increased risk of the development of congenital malformations, including NTDs. This article reviews the biochemistry of FRs, the factors regulating FR scavenging capacity, and the theories regarding the etiology of NTDs; presents a hypothesis of a unified mechanism for AED-induced NTDs and other congenital defects; and briefly discusses the roles of folate and selenium in the prevention of NTDs.
authors.affiliation: Department of Biomedical and Health Sciences, Grand Valley State University, Allendale, Michigan, USA. cepip@iserv.net
authors.forename: C E
authors.initials: CE
authors.lastname: Pippenger
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000009:adverse effects* / Q000138:chemical synthesis; D006801:Humans; D007231:Infant, Newborn; D009436:Neural Tube Defects / Q000139:chemically induced*; D011247:Pregnancy
chemical_list: D000927:Anticonvulsants; D016166:Free Radical Scavengers; D005609:Free Radicals