Impaired methionine synthesis and hypomethylation in rats exposed to valproate during gestation

摘要: Article abstract-Background: The antiepileptic drug valproic acid (VPA) may be teratogenic. mechanism of teratogenicity remains unclear, but it has been hypothesized that VPA interferes with folate metabolism. Objective: To study the effect on methionine cycle and transmethylation reactions in pregnant rats. Methods: Wistar rats were treated (300 mg/kg/day) gestation days 8, 9, 10, alone or combination folinic (FOL, 4 10 S-adenosylmethionine (SAM, throughout 1 to 10. Results: induced a reduction maternal serum concentration (p < 0.05) caused by 24% synthase activity liver. This provoked hepatic DNA hypomethylation, although methylation ratio (S-adenosylmethionine/S-adenosylhomocysteine was not altered. Homocysteine, folate, vitamin B 12 concentrations, as well adenosyltransferase betaine homocysteine methyltransferase activities, did change. In fetuses exposed VPA, no observed content, reduced 0.01), leading again hypomethylation. Coadministration FOL prevented VPA-induced alterations synthesis corrected fetal By contrast, SAM exert protective methylation. Conclusion: Impaired hypomethylation involved teratogenesis.