Schulpis Kleopatra H, Lazaropoulou Christina, Regoutas Spyros, Karikas George A, Margeli Alexandra, Tsakiris Stylianos, Papassotiriou Ioannis
Institute of Child Health, Research Center Athens, Athens, Greece.
Toxicology. 2006 Jan 16;217(2-3):228-32. doi: 10.1016/j.tox.2005.10.004. Epub 2005 Nov 14.
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.
丙戊酸（VPA）和8-羟基-2-脱氧鸟苷（8-OHdG）与自由基的产生有关。我们旨在评估接受VPA单药治疗的儿童的总氧化剂状态（TOS）和8-OHdG。50例癫痫患儿，平均年龄8.5±3.6岁，分为A组（N = 26）和B组（N = 24），VPA血清水平分别为81.0±8.0和114±9.7μg/mL。30名健康儿童作为对照。在VPA治疗60天后，用常规方法测定肝功能试验和血脂，用商业试剂盒测定TOS和8-OHdG。B组的肝功能参数、血脂、TOS（647±43μmol/L）和8-OHdG（0.49±0.08 ng/mL）显著高于A组（580±40μmol/L，0.37±0.04 ng/mL，p<0.001）和对照组（124±30μmol/L，0.11±0.04 ng/mL，p<0.001）。8-OHdG与TOS（r = 0.67，p<0.001）以及8-OHdG与VPA（r = 0.60，p<0.001）水平之间存在显著的相关系数。提示VPA损害肝功能导致自由基产生。后者似乎在肝细胞中产生DNA氧化损伤，不排除神经元细胞，这从测得的8-OHdG血清水平显著升高得到证明。8-OHdG评估可能是一种有用的生物标志物，用于随访VPA患者退变过程增加的风险。
