Study of Phenytoin Effect on the genes involved in glucose and lipid metabolism expression in liver: A mouse model study

Abstract

Phenytoin as an anti-seizure medication, is useful for the prevention of tonic-clonic seizures and focal seizures. In this study we focused on the probable effects of Phenytoin drug on gene expression profile of liver related to lipid metabolism balance in mouse as a model. In this study, a group including 7 male mice of BALB/c were treated with phenytoin 3-5 mg/kg/day orally and a group including 7 male mice of BALB/c were took standard food. Liver tissue samples were isolated. Total RNA was extracted and cDNA was synthesized. Expression of Akt1, Leptin, Adipoq and GLUT4 genes was measured using Realtime RT-PCR method. Results showed an increase about 15 and 3 fold changes in Akt1 (P <0.001) and Adipoq (P <0.001) gene expression respectively in treatment group compare to control mice. Also, we detected decreasing in Leptin and GLUT4 genes expression in the mice treated with phenytoin drug. Several studies indicated that phenytoin can promote hyperglycemia in human and animal. We proposed here that this effects may resulted from an interference between the phenytoin drug and gene expression profile in liver. Decreasing of leptin level here may be a result of glucose level elevation in blood that can induce a satiety situation result in decrease of leptin production. It may that Akt1 gene expression is increased to compensate the low level of GLUT4 protein. We concluded that phenytoin is a relatively high-risk antiepileptic drug for obesity and metabolic syndrome, but more studies are needed.