title: Valproic acid monotherapy induces DNA oxidative damage.
abstract: Valproic acid (VPA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) are implicated with the free radicals production. We aimed to evaluate total oxidant status (TOS) and 8-OHdG in children on VPA monotherapy. Fifty patients with seizures, mean age 8.5+/-3.6 years, were divided into group A (N=26) and group B (N=24) with VPA serum levels 81.0+/-8.0 and 114+/-9.7 microg/mL, respectively. Thirty healthy children were the controls. Liver function tests and lipids were determined with routine methods, TOS and 8-OHdG with commercial kits, after 60 days on VPA therapy. Liver function parameters, lipids, TOS (647+/-43 micromol/L) and 8-OHdG (0.49+/-0.08 ng/mL) were significantly higher in group B than those in group A (580+/-40 micromol/L, 0.37+/-0.04 ng/mL, p<0.001) and controls (124+/-30 micromol/L, 0.11+/-0.04 ng/mL, p<0.001, respectively). Significant correlation coefficients were found between 8-OHdG versus TOS (r=0.67, p<0.001) and 8-OHdG versus VPA (r=0.60, p<0.001) levels. It is suggested that VPA impairs the liver function resulting in free radicals production. The latter seems to produce DNA oxidative damage in liver cells, not excluding neuronal cells, as evidenced by the measured remarkably increased 8-OHdG serum levels. 8-OHdG evaluation may be a useful biomarker to follow up the increased risk of degeneration process in VPA patients.
authors.affiliation: Institute of Child Health, Research Center Athens, Athens, Greece.
authors.forename: Kleopatra H
authors.initials: KH
authors.lastname: Schulpis
authors.forename: Christina
authors.initials: C
authors.lastname: Lazaropoulou
authors.forename: Spyros
authors.initials: S
authors.lastname: Regoutas
authors.forename: George A
authors.initials: GA
authors.lastname: Karikas
authors.forename: Alexandra
authors.initials: A
authors.lastname: Margeli
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D016877:Oxidants / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D012640:Seizures / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants; D014635:Valproic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine