Oxidative stress in children receiving valproic acid

Objective. To determine whether valproic acid (VPA) influences urinary levels of 15-F-2t-isoprostane (15-F-2t-IsoP), a marker of oxidative stress, in children. Study design. Morning urine samples were collected from children with epilepsy receiving VPA (n = 25), carbamazepine (n = 16), or clobazam (n = 12) for >= 4 weeks and from age-matched control subjects (n = 39). Urinary 15-F-2t-IsoP levels were determined by enzyme-linked immunosorbent assay. Results. The mean (standard deviation) urine 15-F-2t-IsoP levels (nmol/mmol Cr) were: valproic acid (0.36 +/- 0.15); carbamazepine (0.24 +/- 0.10); clobazam (0.23 +/- 0.10); control group (0.20 +/- 0.09). Patients treated with VPA had significantly elevated 15-F-2t-IsoP levels when compared with the control, carbamazepine, and clobazam groups (P < .05). Multiple linear regression analysis demonstrated that younger patient age and exposure to second-hand smoke were significant predictors of elevated urine 15-F-2t-IsoP levels within the control group (r(2) = 0.261, P = .05 and P = .01, respectively). Subjects not exposed to second-hand smoke receiving valproic acid therapy had a significantly elevated mean urine 15-F-2t-IsoP level compared to subjects not exposed to second-hand smoke in the carbamazepine, clobazam and control groups (P < .05). Conclusions. These data demonstrate that treatment of children with VPA is associated with higher urinary levels of 15-F-2t-IsoP, a marker of oxidative stress.