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.

Untangling the oxidative cost of reproduction: An analysis in wild banded mongooses

“…Interestingly, a previous study conducted on banded mongooses has found evidence that supports the oxidative shielding hypothesis, with breeders displaying lower levels of oxidative damage to lipids compared to non-breeders. Moreover, that same study, along with a few others, have found that maternal oxidative stress during breeding can negatively impact offspring production and development (Bize et al, 2008;Dupoué et al, 2020;Essa et al, 2015;Møller et al, 2008;Vitikainen et al, 2016). Although mechanisms of shielding are not yet well understood, presumably mothers incur some costs through damage reduction (e.g., by upregulation of antioxidant defenses); otherwise, it would be expected that oxidative damage should be maintained at low levels all of the time.…”

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

“…Related studies have indicated that antioxidant treatments can prevent or reduce growth retardation and/or the occurrence of malformations as a consequence of xenobiotics exposure during development [51]. In line with the use of antioxidant and folic acid therapy for reduction of the frequency and severity of AEDinduced teratogenic effects, it was found that concomitant vitamin E administration significantly attenuated valproic acid and phenytoin induced decrease in crown-rump length, fetal weight and malformations [26,28,39]. The study of Abd El-Aziz et al [36] showed that the co-administration of vitamin E with MeHg was also associated with an improvement in the fetal crown-rump length, body weight, head length, and biparietal diameter of the rat fetuses.…”

“…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].…”