ALTERED ANTIOXIDANT ENZYME-ACTIVITIES IN CHILDREN WITH A SERIOUS ADVERSE EXPERIENCE RELATED TO VALPROIC ACID THERAPY

Specific oxidative metabolites of valproic acid (VPA) have been associ ated 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 he althy, age-matched subjects. These enzymes included glutathione peroxi dase (GSH-Px), glutathione reductase (GSSG-R), glutathione transferase , superoxide dismutase, and catalase in erythrocytes; and GSH-Px in pl asma. We also determined levers of Se, Cu, and Zn, trace elemental cof actors for these enzymes, in plasma from each individual. In patients with a VPA-associated SAE, GSH-Px was significantly depressed and GSSG -R was significantly elevated relative to values for the other groups. Selenium and zinc concentrations were lower in SAE patients than in c ontrols. These findings may indicate a role for selenium dependent ant ioxidant activity in individual susceptibility to an SAE related to VP A therapy.