The Effects of Carvedilol and Vitamin E on Sodium Valproate-Induced Skeletal Teratogenicity in Rat Fetuses

Sodium valproate, an anticonvulsant drug, has teratogenic effects on humans’ and animals’ skeletal system via causing free radicals and oxidative stress. Carvedilol has beta-blocker, antioxidant and anti-inflammatory effects and was the benefit in diseases such as diabetes and renal failure and has protective effect in experimental oxidative stress models. The aim of this study was to compare the roles of carvedilol and vitamin E (a well-known antioxidant) in reducing or preventing skeletal abnormalities from sodium valproate in rat fetuses.
This study was performed on 30 pregnant rats in four groups. On 8th and 9th days of pregnancy, for first (control) to fourth groups, intraperitoneal normal saline, sodium valproate (300 mg/kg), sodium valproate (300 mg/kg) plus carvedilol (5 mg/kg), and valproate sodium (300 mg/kg) plus vitamins E (100 mg/kg) were administrated, respectively. On the 20th day of pregnancy, all rats were euthanized and fetuses were extracted. Weight and height were determined, skeletal system samples were stained by Alizarin red-alcian blue method, and skeletal system was examined by stereomicroscope.
Findings: In fetuses of sodium valproate group, the incidence rates of exencephaly, cleft palate, spina bifida, and omphalocele were 14.58%, 14.58%, 16.66%, and 10.41%, respectively. However, it decreased to 6.55%, 8.19%, 6.55%, and 8.19% by carvedilol and so to 3.5%, 8.75%, 3.5%, and 3.5% by vitamin E, respectively. The mean length of fetuses in sodium valproate group plus carvedilol and sodium valproate plus vitamin E was significantly less than the mean length in the control group but did not have significant differences with each other. The mean fetal weight in sodium valproate plus vitamin E group was significantly more than sodium valproate and sodium valproate plus carvedilol, although it was lower than the control group.
Carvedilol and vitamin E had similar effects on fetal skeletal abnormality and changes of fetal length caused by sodium valproate; but vitamin E was more protective against fetal weight changes.