Oxidative stress in children receiving valproic acid.
OBJECTIVE
To determine whether valproic acid (VPA) influences urinary levels of 15-F2t -isoprostane (15-F2t -IsoP), a marker of oxidative stress, in children.


METHODS
Morning urine samples were collected from children with epilepsy receiving VPA (n = 25), carbamazepine (n = 16), or clobazam (n = 12) for > or = 4 weeks and from age-matched control subjects (n = 39). Urinary 15-F2t -IsoP levels were determined by enzyme-linked immunosorbent assay.


RESULTS
The mean (+/- standard deviation) urine 15-F2t -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-F2t -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-F2t -IsoP levels within the control group (r2 = 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-F2t -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-F2t -IsoP, a marker of oxidative stress.
Michoulas
Aspasia
A
Division of Neurology, Department of Pediatrics, and the Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Tong
Vincent
V
Teng
Xiao Wei
XW
Chang
Thomas K H
TK
Abbott
Frank S
FS
Farrell
Kevin
K
D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine; D001569:Benzodiazepines / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D002170:Canada; D002220:Carbamazepine / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D003404:Creatinine / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011237:Predictive Value of Tests; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine
D000927:Anticonvulsants; D015415:Biomarkers; D014028:Tobacco Smoke Pollution; D001569:Benzodiazepines; C075750:8-epi-prostaglandin F2alpha; D000078306:Clobazam; D002220:Carbamazepine; D014635:Valproic Acid; D003404:Creatinine; D015237:Dinoprost