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

George A Karikas1, Kleopatra H Schulpis, Anastasia Bartzeliotou

  • 1Department of Medical Laboratories, Technological and Educational Institute of Athens, Athens, Greece.

Scandinavian Journal of Clinical and Laboratory Investigation
|November 19, 2008
PubMed

Insights

Valproic acid (VPA) treatment in children significantly decreased paraoxonase-1/arylesterase (PON1/Aryl) activities. This reduction is linked to increased oxidative stress and potential liver dysfunction from VPA therapy.

Area of Science:

  • Biochemistry
  • Pediatric Neurology
  • Pharmacology

Background:

  • Valproic acid (VPA) is an anticonvulsant medication used in treating epilepsy.
  • VPA treatment is associated with oxidative stress and potential alterations in antioxidant enzyme activity.
  • Paraoxonase-1/arylesterase (PON1/Aryl) is a key antioxidant enzyme involved in protecting against lipid peroxidation.

Purpose of the Study:

  • To investigate the impact of VPA therapy on PON1/Aryl activities in children.
  • To explore the relationship between VPA treatment, oxidative stress markers, and PON1/Aryl levels in pediatric patients.

Main Methods:

  • A study involving 32 children with seizures undergoing VPA therapy and 30 healthy controls.
  • Biochemical analyses included total antioxidant status (TAS), total oxidant status (TOS), lipid profile, liver enzymes, and PON1/Aryl activities.
  • Measurements were taken before and after 60 days of VPA treatment in the patient group.

Main Results:

  • No significant biochemical differences were observed between controls and pre-treatment patients.
  • VPA treatment led to significantly elevated liver enzymes and TOS levels.
  • PON1/Aryl activities and TAS levels were significantly decreased post-VPA treatment.
  • Negative correlations were found between PON1/Aryl activities and VPA levels/TOS, and positive correlations with TAS/HDL/Apo A-I.

Conclusions:

  • Serum PON1/Aryl activities are reduced following 60 days of VPA treatment in children.
  • The decrease in PON1/Aryl activity is likely due to VPA-induced free radical production and potential liver dysfunction.
  • A direct inhibitory effect of VPA on PON1/Aryl enzymes cannot be excluded.
Abstract

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