Prophylactic Effects of Melatonin on Sodium Valproate-Induced Neural Tube Defects and Skeletal Malformations in Rat Embryos

Abstract

Problem statement: Some reports showed the teratogenic effects of sodium valproate can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Therefore, in this study, the prophylactic effect of melatonin on teratogenic effects of sodium valproate was compared. Approach: This study was performed on 31 pregnant rats that were divided into five groups. Control group received normal saline and test groups received sodium valproate (300 mg kg⁻¹), sodium valproate (300 mg kg⁻¹) plus melatonin (5 mg kg⁻¹) and sodium valproate (300 mg kg⁻¹) plus melatonin (10 mg kg⁻¹) and melatonin (10 mg kg⁻¹), intraperitonealy at 8-9th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Results: Cleft palate, spina bifida and exencephaly incidence were 17.70, 20 and 20% in fetuses of rats that received only sodium valproate. Cleft palate, spina bifida and exencephaly incidence were 4.16, 8.33 and 8.33% range in group which received sodium valproate plus melatonin (5 mg kg⁻¹), respectively. However, Cleft palate, spina bifida and excencaphaly incidence were 4/76, 0 and 0% in group which received sodium valproate plus melatonin (10 mg kg−1), respectively. The mean of weight and length of animals’ fetuses that received melatonin were significantly greater than those received only sodium valproate. Conclusion: It is concluded that melatonin with dose of 10 mg kg⁻¹ had significantly more prophylactic effect than melatonin with dose of 5 mg kg−¹ on incidence of sodium valproate-induced skeletal malformations.