Early effects of sodium valproate monotherapy on serum paraoxonase/arylesterase activities

Objective . Valproic acid (VPA) treatment and paraoxonase1/arylesterase (PON1/Aryl) activities are related to the production of free radicals. Our aim was to study the PON1/Aryl activities in children on VPA therapy. Material and methods . Thirty-two children with seizures and 30 healthy child volunteers took part. Ill children underwent the common laboratory tests, as well as total antioxidant status (TAS), total oxidant status (TOS), lipid profile, liver enzymes and PON1/Aryl activities pre- and post-60 days on VPA therapy (30 mg/kg/24 h), whereas the healthy children were tested just once. Results . None of the studied biochemical parameters differed between volunteers and children with seizures pretreatment. Liver enzymes, lipids and TOS levels (12430 versus 58040 mol/L; p0.001) were significantly elevated, whereas the activities of PON1/Aryl (14643 versus 11840 U/mL/min 12042 versus 9838 KU/mL/min; p0.01) and TAS levels (43642 versus 28839 mol/L; p0.001) were decreased in children after treatment. Additionally, strong negative correlations were found between PON1/Aryl activities, liver enzymes, TOS (r=-0.69) and VPA levels (r=-0.57), whereas PON1/Aryl activities correlated positively with TAS, HDL and Apo A-I in all groups. Conclusions . Serum PON1/Aryl activities were decreased after 60 days on VPA treatment, probably due to liver dysfunction and free radicals production by VPA, without excluding the possibility of a direct action of the drug on the enzymes.