Teratogenic effects of sodium valproate in mice and rats at midgestation and at term

Menegola, Elena; Broccia, Maria Luisa; Nau, Heinz; Prati, Mariangela; Ricolfi, R.; Giavini, Erminio

doi:10.1002/(sici)1520-6866(1996)16:2<97::aid-tcm4>3.0.co;2-a

Cited by 71 publications

(64 citation statements)

References 17 publications

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“…Gestation outcome. The same effect has been previously described, 7,9 and it has been suggested that these axial skeleton malformations may be secondary to the action of VPA on the neural plate because of the developmental interdependence of the neural plate and the paraxial mesoderm. In other studies, a single dose of 300 mg/kg on gestation day 8 has produced a 1.2% to 12.7% response frequency of exencephaly in mice.…”

supporting

confidence: 77%

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Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation

et al. 1999

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supporting

confidence: 77%

“…6,8,9 Therefore, rats seem to be more resistant than mice to VPA-induced teratogenesis, an interspecies effect that has been poorly studied. Gestation outcome.…”

mentioning

confidence: 99%

Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation

et al. 1999

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“…As for VPA, kinked notochord, rhexis of notochord, and lower jaw anomalies were observed in larval zebrafish in mammals (Menegola et al, 1996;Ornoy, 2006). This evidence indicates that some teratogenic phenotypes that to the in vivo mammalian phenotypes.…”

Section: Discussionmentioning

confidence: 70%

Improvement of the evaluation method for teratogenicity using zebrafish embryos

et al. 2014

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ABSTRACTcially for evaluation of the teratogenicity, due to their small size, rapid development, transparency, and maintain them in culture plates, evaluate the teratogenicity in short term, conduct morphological assessment of each organ without any autopsy operation. The purpose of the present study was to improve an evaluation method for the teratogenicity of test compounds with high throughput ability and prediction -were exposed to test compounds from 5-6 to 144 hr post-fertilization, (hpf) corresponding to the organogenesis period. Morphological changes or functional abnormalities induced by test compound treatments were assessed and scored at 11 endpoints, and the potential of teratogenicity was judged based on the score. As a validation assay of the system, the potentials of 59 known teratogenic or non-teratogenic test -rectly predicted in 90% (53/59) of all compounds with low false negative and false positive rates. These valuable tool for early stage screening in drug discovery.

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“…VPA treatment during early neural tube formation (E8 in the mouse) results in exencephaly, which is the rodent equivalent of human anencephaly. Others reported that spina bifida can be induced in some mouse strains when injected three times at 6-h intervals on E9 [Ehlers et al, 1992;Emmanouil-Nikoloussi et al, 2004;Finnell et al, 1988;Menegola et al, 1996]. Pharmacokinetic study showed that VPA can induce neural tube defects in exposed mouse embryos when this drug reaches maternal plasma concentrations of 225 μg/ml, irrespectively of the route of administration [Nau, 1985].…”

Section: Phenobarbital (Solfoton)mentioning

confidence: 99%

Antiepileptic Drugs and Pregnancy Outcomes

Wlodarczyk

Palacios

George³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos.

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Teratogenic effects of sodium valproate in mice and rats at midgestation and at term

Cited by 71 publications

References 17 publications

Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation

Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation

Improvement of the evaluation method for teratogenicity using zebrafish embryos

Antiepileptic Drugs and Pregnancy Outcomes

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