Phenytoin (dilantin)‐induced cleft lip and palate in a/j mice: A scanning and transmission electron microscopic study

Sulik, Kathleen K.; Johnston, Malcolm C.; Ambrose, L. Jeannie H.; Dorgan, D.

doi:10.1002/ar.1091950201

Cited by 60 publications

(21 citation statements)

References 7 publications

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“…[46][47][48] Moreover, our study showed maxillary hypoplasia in 13.79% of pups in PHT-treated group. This is in agreement with the finding of Abela et al [16] However, Sulik et al [49] reported that PHT increased incidence of cleft lip (CL) of strains of mice with genetic predisposition to malformation. Furthermore, it has been reported that genetic predisposition is enhanced by maternal hypoxia and reduced by maternal hyperoxemia.…”

Section: Discussionsupporting

confidence: 92%

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

Essa¹,

Gabr²,

Mohamed³

et al. 2015

Anatomy

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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.

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Section: Discussionsupporting

confidence: 92%

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

Essa¹,

Gabr²,

Mohamed³

et al. 2015

Anatomy

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“…The homeotic gene Msx-1 (Hox-7) may be involved (MacKenzie et al, 1991a,b), as noted above, Pax-6 is expressed in the placode, and Pax-3 in the prominence mesenchyme (Goulding et al, 1991). Such interactions may be mediated by a mesenchymal cell process meshwork (Sulik et al, 1979).…”

Section: (L):25-79 (1995)mentioning

confidence: 99%

Prenatal Craniofacial Development: New Insights On Normal and Abnormal Mechanisms

Johnston

Bronsky²

1995

Critical Reviews in Oral Biology & Medicine

115

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Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through ceil migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules, "growth factors" (e.g., FGF and TGFoc) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues.Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGFocs, RARocs, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent "mismatches" found in malocclusions and other dentofacial "deformities".Future directions for research, including possibilities for prevention, are discussed.

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“…The subepithelial cell process meshwork has also been implicated as playing a significant role in developmental phenomena (Sulik et al, 1979;Igawa et al, 1986). It is, therefore, possible that the interaction of the maxillary mesenchyme with the maxillary epithelium, in terms of cell survival, may be mediated by a more complex "inductive system" at the epithelial-mesenchymal interface composed not only of a basal lamina but of a cell process meshwork and, potentially, other components as well.…”

Section: Discussionmentioning

confidence: 99%

Influence of epithelial‐mesenchymal interaction on the viability of facial mesenchyme in vitro

1989

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Separation and recombination experiments, employing a variety of tissue configurations in organ culture, were performed to determine the extent to which the epithelium of the maxillary process influences the viability of the underlying mesenchyme during organogenesis. The results of these studies indicated that the viability of mesenchyme of the maxillary process of early stage embryos was severely impaired when separated from the overlying epithelium. The influence of epithelium on the viability of mesenchyme was stage dependent; that is, the requirement for the presence of epithelium for the maintenance of the viability of mesenchyme became progressively less pronounced at older developmental stages. The response of mesenchyme to the presence of recombined epithelium resulted in the appearance of a delimited zone of influence extending, within specific boundaries, from the epithelial-mesenchymal interface. Preliminary data from homotypic (maxillary epithelium-maxillary mesenchyme), heterotypic (limb apical ectodermal ridge-maxillary mesenchyme) and heterochronic (stage 28 epithelium-stage 22 mesenchyme) recombination experiments indicated that viability of mesenchyme could be achieved only through direct epithelial-mesenchymal contact which allowed restoration of normal morphological relationships at the interface of the two tissues.

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Phenytoin (dilantin)‐induced cleft lip and palate in a/j mice: A scanning and transmission electron microscopic study

Cited by 60 publications

References 7 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

Prenatal Craniofacial Development: New Insights On Normal and Abnormal Mechanisms

Influence of epithelial‐mesenchymal interaction on the viability of facial mesenchyme in vitro

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