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Neuropediatrics 1998; 29(4): 195-201
DOI: 10.1055/s-2007-973560
Original articles

© Hippokrates Verlag GmbH Stuttgart

Altered Antioxidant Enzyme Activities in Children with a Serious Adverse Experience Related to Valproic Acid Therapy

W. D. Graf1 , 2 , O. E. Oleinik1 , T. A. Glauser4 , P. Maertens5 , D. N. Eder3 , C. E. Pippenger6
  • 1Departments of Pediatrics University of Washington, Seattle WA;
  • 2Departments of Neurology University of Washington, Seattle WA;
  • 3Departments of Psychology University of Washington, Seattle WA;
  • 4Department of Neurology, Children's Hospital Medical Center, Cincinnati OH;
  • 5Department of Neurology, University of South Alabama, Mobile AL;
  • 6FRESA BioMedical Laboratories, Redmond WA, USA
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Publication History

Publication Date:
12 March 2007 (online)

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Abstract

Specific oxidative metabolites of valproic acid (VPA) have been associated with the clinically defined toxicity of the drug. To investigate the role of enzymatic detoxification in clinical toxicity, we compared activities of five antioxidant enzymes in 15 patients with a serious adverse experience (SAE) related to VPA therapy, to enzyme activities measured in 35 patients with good clinical tolerance of VPA, and 50 healthy, age-matched subjects. These enzymes included glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione transferase, superoxide dismutase, and catalase in erythrocytes; and GSH-Px in plasma. We also determined levels of Se, Cu, and Zn, trace elemental cofactors for these enzymes, in plasma from each individual. In patients with a VPA-associated SAE, GSH-Px was significantly depressed and GSSC-R was significantly elevated relative to values for the other groups. Selenium and zinc concentrations were lower in SAE patients than in controls. These findings may indicate a role for selenium dependent antioxidant activity in individual susceptibility to an SAE related to VPA therapy.

Key words

Valproic acid - Selenium - Clutathione peroxidase - Antioxidants - Glutathione