Genotoxity evaluation in female patients on valproic acid monotherapy using alkaline single cell gel electrophoresis

Valproic acid is a commonly used antiepileptic drug for chronic therapy and may have adverse effects on gastrointestinal, hematologic and nervous system. Potential mutagenic effects of sodium valproate have been reported, but this effect of valproic acid has still not been clarified yet. Comet assay was performed in peripheral lymphocytes of 24 epileptic adolescent and adult female treated with valproic acid monotherapy for at least one year and in a control group including 16 adolescent and adult healthy, drug free females. The frequencies of comet scores in the valproic acid treated epileptic patients were significantly higher than that of the control group (p<0.05) indicating a detectable chromosome damaging effect of valproic acid monotherapy on human lymphocytes. No significant correlation was noted amongst age, drug dose, blood valproic acid levels, duration of valproic acid therapy and the comet scores. Although genotoxic effects of valproic acid was shown by means of sister chromatid exchange and chromosomal aberration assays in previous studies, we report here the first demonstration of genotoxic potential of valproic acid with comet assay. This data supports the conclusion that valproic acid is genotoxic.