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

Soysal, Handan; Unur, Erdoğan; Düzler, Ayhan; Karaca, Oğuz; Ekinci, Nihat

doi:10.1016/j.seizure.2010.12.009

Cited by 17 publications

(16 citation statements)

References 21 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Harbison and Becker [53] and Mansoor et al [56] have reported a worsening in the ossification process of the long bones in the mouse and rat fetuses of the PHT treated mothers, but such a finding was not observed in the present work. Soysal [13] and Mansoor et al [56] reported costal anomalies in the form of costal separation, while Kim et al [55] have reported costal anomalies in the form of absent, short and discontinuous ribs, and absent ossification of some sternebrae in the fetuses of PHT treated rats. However, our study showed absence of ossification centre of one sternebra and costal separation in the pups of the PHT-treated mothers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protective effect of maternal vitamin E supplementation on phenytoin-induced teratogenicity in rat pups

Essa¹,

Gabr²,

Mohamed³

et al. 2015

Anatomy

View full text Add to dashboard Cite

Objectives: Phenytoin teratogenicity is induced by embryonic hypoxia as a result of generation of reactive oxygen species. Antioxidants are effective in treating conditions associated with oxidative damage. This study investigated the possible protective effect of vitamin E maternal supplementation on oxidative damage, and the morphological and morphometric changes induced by phenytoin in pups.Methods: Five groups of female rats were utilized. All the treatments were injected intraperitoneal. Groups I and II were injected with saline and olive oil, respectively. Group III was injected with vitamin E (0.5 g/kg BW/day) from day one to day 20 of gestation. Group IV was injected with phenytoin (150 mg/kg BW/day) from day 6 to day 18 of gestation. Group V was injected with phenytoin and vitamin E. The N-acetyl D-glucosaminidase, malondialdehyde, and glutathione were determined as markers of tissue damage. The skeletons of pups were examined after staining with alizarin red-S.Results: Phenytoin significantly increased oxidative stress indices in maternal plasma and tissues and in pup tissues. This was associated with a significant decrease in the weight, length and number of pups. Moreover, there were maxillary hypoplasia and skeletal anomalies. Co-administration of vitamin E with phenytoin reduced oxidative damage with significant increase in the weight, length and number of pups. Reduction in maxillary hypoplasia and skeletal anomalies were observed. Conclusion:Vitamin E maternal supplementation has significant effect in the reduction of the anomalies induced by phenytoin in pups.

show abstract

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11][12] PHT has been documented to be a teratogenic agent in both mice and rats. [13] It is believed that PHT produces anomalies in 34% of fetuses which are exposed to it. [14] Cleft lip (CL) is a common malformation that has both genetic and exogenous causes.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of maternal vitamin E supplementation on phenytoin-induced teratogenicity in rat pups

Essa¹,

Gabr²,

Mohamed³

et al. 2015

Anatomy

View full text Add to dashboard Cite

show abstract

“…Soysal et al (17) using 25mg/kg/day phenytoin administered intraperitoneally to pregnant rats detected that fetuses were 14% shorter and the weights 13% lower compared to control animals with decreased number of the fetuses obtained in one gestation by 9%, and deteriorated ossification of skull bones, costal separation anomaly, the laterally-separated costal components were not attached to the costal arch with shape malformations in the last two ribs and wide angularity, particularly in the last six ribs.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats

Salam¹,

Allam²

2015

IJCDA

View full text Add to dashboard Cite

Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.

show abstract

“…Mice and rats exposed to valproic acid exhibited abnormal limbs including long bone reductions and abnormal or missing digits [25,27,28,38]. Similarly, rat fetuses maternally subjected to intraperitoneal injection of phenytoin suffered from deteriorated ossification of skull bones and costal separation anomaly [2,39].…”

Section: Gbp + Ginger Groupmentioning

confidence: 99%

“…Due to relapsing and severity of epilepsy, many women cannot stop using medications even during pregnancy [1]. It is a well-documented fact that teratogens affect the development of embryo, mostly during the process of organogenesis, which starts on GD 6 in rats and continues to GD 15 [2]. Currently, management of epilepsy mainly depends on antiepileptic drugs (AEDs), which are notoriously known for their adverse side effects and this explains the reason for their several generations.…”

Section: Introductionmentioning

confidence: 99%

Morphological and Skeletal Malformations Induced by Gabapentin in Rat Fetuses and their Amelioration by Ginger

Badawy¹,

Atallah²,

Sakr³

2019

AJABS

View full text Add to dashboard Cite

The present study aimed to investigate the possible morphological and skeletal fetotoxicity of the new antiepileptic drug, gabapentin (GBP) during the organogenesis phase of the rat embryonic development and to examine the possible ameliorative role of ginger (Zingiber officinale). Morphologically, there was evident growth retardation and a high frequency of malformations in the skin, head, trunk, limbs and tail of fetuses maternally injected with GBP. Skeletal investigation revealed that rat fetuses of the GBP group exhibited delayed ossification and various skeletal malformation. Limb deformities was the most prominent feature observed followed by coastal malformations, vertebral deformities, skull anomalies and sternal defects, respectively. The most evident skull malformation was maxillary and mandibular hypoplasia. Ginger extract caused an evident decrease in GBP-induced fetotoxicity at the investigated parameters. In conclusion, treatment with GBP should be approached with highly caution during pregnancy and ginger is recommended to be taken in parallel for its ameliorative role in this regard.

show abstract

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

Cited by 17 publications

References 21 publications

Protective effect of maternal vitamin E supplementation on phenytoin-induced teratogenicity in rat pups

Protective effect of maternal vitamin E supplementation on phenytoin-induced teratogenicity in rat pups

The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats

Morphological and Skeletal Malformations Induced by Gabapentin in Rat Fetuses and their Amelioration by Ginger

Contact Info

Product

Resources

About