Genotoxicity Evaluation in Female Patients On Valproic Acid Monotherapy Using Alkaline Single Cell Gel Electrophoresis (Comet Assay)

Abstract

Valproic acid is a commonly used antiepileptic drugfor chronic therapy and may have adverse effects ongastrointestinal, hematologic and nervous system.Potential mutagenic effects of sodium valproate havebeen reported, but this effect of valproic acid has stillnot been clarified yet. Comet assay was performed inperipheral lymphocytes of 24 epileptic adolescent andadult female treated with valproic acid monotherapyfor at least one year and in a control group including16 adolescent and adult healthy, drug free females. Thefrequencies of comet scores in the valproic acid treatedepileptic patients were significantly higher than thatof the control group (p<0.05) indicating a detectablechromosome damaging effect of valproic acidmonotherapy on human lymphocytes. No significantcorrelation was noted amongst age, drug dose, bloodvalproic acid levels, duration of valproic acid therapyand the comet scores. Although genotoxic effects ofvalproic acid was shown by means of sister chroma-tid exchange and chromosomal aberration assays inprevious studies, we report here the first demonstra-tion of genotoxic potential of valproic acid with cometassay. This data supports the conclusion that valproicacid is genotoxic.Keywords: Valproic acid, epilepsy, alkaline comet assay,genotoxicity