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

Abstract

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. 

Keywords

• maxillary hypoplasia
• oxidative stress
• phenytoin
• rats
• skeletal anomalies

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64. nal vitamin E supplementation on phenytoin-induced teratogenicity in rat pups. Anatomy 2015;9(1):1–12.