The modifying effect of folinic acid on diphenylhydantoin-induced teratogenicity in mice

Schardein, James L.; Dresner, Alan; Hentz, D.L.; Petrere, Judith A.; Fitzgerald, James E.; Kurtz, Stanley M.

doi:10.1016/0041-008x(73)90190-7

Cited by 34 publications

(5 citation statements)

References 30 publications

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“…In rodents, folk acid-deficient diets or administration of folic acid analogs and antagonists have induced cleft palate as well as other anomalies (Tuchmann-Duplessis and Lefebvres-Boisselot, 1951;Monie et al, 1961;Wilson and Fradkin, 1967). Schardein et al ( 1973) demonstrated that the administration of folinic acid intramuscularly did not significantly reduce the incidence of cleft palate in mice receiving teratogenic doses of DPH. However, serum levels of folic acid were not monitored in maternal mice and, therefore, no conclusion can be drawn as to whether folinic acid was ineffective or whether serum levels were adequate.…”

Section: Discussionmentioning

confidence: 97%

Phenytoin: An Evaluation of Several Potential Teratogenic Mechanisms

1977

Epilepsia

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The effect of pharmacological doses of phenytoin (DPH) administered for a maximum of 28 days was studied in pregnant and nonpregnant rats as well as in 14- and 21-day fetuses. The following parameters were monitored in the adult rats: maximal electroshock seizures, serum DPH and folate, liver microsomal P-450, and 14C-DPH tissue distribution. 14C-DPH distribution was also evaluated in fetal tissues. Pregnant animals demonstrated an increase in anticonvulsant activity as well as increased serum concentrations of DPH throughout pregnancy and on the 7th post-partum day. Brain concentrations of DPH increased during pregnancy but had returned to the values in the nonpregnant group at the 7th post-partum day. Liver microsomal P-450 was decreased in pregnant animals receiving DPH at days 7 and 14 of pregnancy. Serum folate also decreased at day 14 of pregnancy in animals receiving DPH. Fetal tissue binding of DPH appeared to be related to serum concentrations of the drug at day 14. Teratogenic effects of DPH could be related to the increased serum and tissue concentrations of the drug observed during pregnancy as well as its effect on serum folate at day 14 of gestation.

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Section: Discussionmentioning

confidence: 97%

Phenytoin: An Evaluation of Several Potential Teratogenic Mechanisms

1977

Epilepsia

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“…Schardein has also injected phenytoin to mice on the 11th-13th days of the pregnancy. 25 Harbison has given phenytoin to pregnant mice within a period from 8th to 14th days of the gestation. 19 Harbison has applied a single daily dose to a mouse group of 6-8 individuals from 7th to 15th days of the gestation.…”

Section: Discussionmentioning

confidence: 99%

“…29 It has also been documented to be a teratogenic agent in both mice and rats. 14,19,25,[29][30][31][32] In these studies, the following common malformations and defects have been observed in the fetuses of pregnant rodents treated with phenytoin; cleft lip and/or palate, hydrocephaly, hydronephrose, and skeleton anomalies including growth retardation in long bones and ectrodactly. 4 In our study, no cleft lip neither cleft palate was seen in the fetuses of the phenytoin treated rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of intraperitoneal administration of the phenytoin on the skeletal system of rat fetus

Soysal

Unur

Düzler

et al. 2011

Seizure

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This study was conducted on determining the effects of phenytoin on the skeletal system of the fetuses of 13 Wistar Albino rats. The female rats were divided into two groups after the vaginal smear test: the group 1 (control group) included 6 individuals, whereas the group 2 (phenytoin group) comprised 7 animals. A dose of 25mg/kg/day phenytoin was administered intraperitoneally to pregnant rats on the 8th-10th days of pregnancy and fetuses were obtained by C-section on the 20th day. A number of 82 fetuses were observed by double staining technique. Their lengths and weights were measured, revealing the statistically significant differences between the two groups (p<0.001). The lengths of the fetuses in the group 2 were determined as to be 14% shorter and the weights 13% lower compared to those in the group 1. Similarly, number of the fetuses obtained in one gestation decreased 9% in the group 2. Ossification of the skull bones in the fetuses of the group 2 was observed eminently to be deteriorated through using dissection microscope and inspection. Costal separation anomaly was observed in the 10 fetuses of the group 2. The separated-laterally located costal components were not attached to the costal arch. Shape malformations in the last two ribs and wide angularity, particularly in the last six ribs, were also determined. This study has documented that intraperitoneal usage of the pheytoin during pregnancy may cause to different skeletal malformations, even with lower doses, in rat fetuses.

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“…El uso de ácido folínico, cuyo compuesto metabólicamente activo es el tetrahidrofolato, ha demostrado reducir la frecuencia de defectos del tubo neural, cuyo riesgo de ocurrencia está incrementado con el uso de MAE (4). Sin embargo, no todos los estudios sustentan que la administración de ácido fólico reduce la teratogenicidad de los MAE, hay evidencia que la administración de ácido fólico con MAE no produjo reducción en la teratogenicidad inducida por fenitoína (18)(19)(20). Una hipótesis más reciente para la deficiencia de folatos es que una concentración plasmática y tisular de homocisteína elevada es la responsable de los defectos congénitos (21).…”

Section: Desarrollo Mecanismos De Teratogenicidad Propuestosunclassified

“…Oxcarbazepina: la prevalencia de anomalías asociadas con la oxcarbazepina se estima en 2,39 %, similar a la población gestante sin epilepsia (12,5). Existe controversia entre la exposición intrauterina a la lamotrigina y la alteración del neurodesarrollo, ya que se ha publicado evidencia a favor y en contra de asociación con autismo y dispraxia (18,32). No se ha establecido relación entre la dosis y el riesgo de defectos congénitos y alteraciones del neurodesarrollo (12,35).…”

Section: Defectos Congénitosunclassified

Defectos congénitos y alteraciones del neurodesarrollo en feto de madre epiléptica

Gómez

Cabrera-Lozada²

2023

Colección Razetti. Volumen XXVIII

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La epilepsia es un trastorno que se presenta en 0,5 % de los embarazos, tiene riesgo aumentado de complicaciones obstétricas que conllevan incremento de la morbimortalidad materna, fetal y perinatal. El feto de madre epiléptica con exposición en utero a medicamentos antiepilépticos (MAE), tiene un aumento marcado del riesgo de defectos congénitos particularmente defectos mayores como los del tubo neural, cardiopatías, queilosquisis, palatosquisis y urogenitales, así como alteraciones del neurodesarrollo como el retraso cognitivo, el autismo y/o dispraxia, el retraso en el desarrollo psicomotor y el retraso en el lenguaje, con varios mecanismos de teratogenicidad propuestos.

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The modifying effect of folinic acid on diphenylhydantoin-induced teratogenicity in mice

Cited by 34 publications

References 30 publications

Phenytoin: An Evaluation of Several Potential Teratogenic Mechanisms

Phenytoin: An Evaluation of Several Potential Teratogenic Mechanisms

Effects of intraperitoneal administration of the phenytoin on the skeletal system of rat fetus

Defectos congénitos y alteraciones del neurodesarrollo en feto de madre epiléptica

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