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 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 chroma-tid exchange and chromosomal aberration assays in
previous  studies, we report here the first demonstra-tion of genotoxic potential of valproic acid with comet
assay. This data supports the conclusion  that valproic
acid is genotoxic.
Keywords: Valproic acid,  epilepsy,  alkaline comet assay,
genotoxicity

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