ABSTRACT
OBJECTIVE: Valproic acid (VPA) treatment and paraoxonase1/arylesterase (PON1/Aryl) activities are related to the production of free radicals. Our aim was to study the PON1/Aryl activities in children on VPA therapy. MATERIAL AND METHODS: Thirty-two children with seizures and 30 healthy child volunteers took part. Ill children underwent the common laboratory tests, as well as total antioxidant status (TAS), total oxidant status (TOS), lipid profile, liver enzymes and PON1/Aryl activities pre- and post-60 days on VPA therapy (30 mg/kg/24 h), whereas the healthy children were tested just once. RESULTS: None of the studied biochemical parameters differed between volunteers and children with seizures pretreatment. Liver enzymes, lipids and TOS levels (124+/-30 versus 580+/-40 micromol/L; p<0.001) were significantly elevated, whereas the activities of PON1/Aryl (146+/-43 versus 118+/-40 U/mL/min 120+/-42 versus 98+/-38 KU/mL/min; p<0.01) and TAS levels (436+/-42 versus 288+/-39 micromol/L; p<0.001) were decreased in children after treatment. Additionally, strong negative correlations were found between PON1/Aryl activities, liver enzymes, TOS (r = -0.69) and VPA levels (r = -0.57), whereas PON1/Aryl activities correlated positively with TAS, HDL and Apo A-I in all groups. CONCLUSIONS: Serum PON1/Aryl activities were decreased after 60 days on VPA treatment, probably due to liver dysfunction and free radicals production by VPA, without excluding the possibility of a direct action of the drug on the enzymes.
Subject(s)
Aryldialkylphosphatase/blood , Carboxylic Ester Hydrolases/blood , Valproic Acid/pharmacology , Antioxidants/metabolism , Case-Control Studies , Child , Child, Preschool , Female , Humans , Lipids/blood , Male , Oxidants/blood , Seizures/blood , Seizures/drug therapy , Seizures/enzymology , Valproic Acid/therapeutic useABSTRACT
BACKGROUND: Over the past decade, it has been well established that elevated total serum homocysteine (tHcy) in adults is associated with increased risk of cardiovascular and thromboembolic diseases. Since risk factors for such diseases are established at a young age, the aim of the present study was to measure serum tHcy levels in 134 (71 boys, 63 girls) randomly selected healthy preschool children aged 4-6 years (mean 5.1), and to investigate possible correlation with paraoxonase 1 (PON1) activity, an antioxidant enzyme that contributes to the antiatherogenic properties of high-density lipoprotein (HDL). METHODS: tHcy was determined using an IMX tHcy assay (FPIA). PON1 was measured by a spectrophotometric method at 412 nm. RESULTS: Mean serum tHcy was 7.71+/-2.35 mumol/L. A relatively significant percentage (15.6%) of boys and girls had elevated serum tHcy levels (>10 mumol/L). tHcy levels were slightly higher in girls compared to boys (8.20+/-2.80 vs. 7.29+/-1.79 mumol/L, respectively; p<0.11). There was no significant interaction between age and tHcy levels. Mean PON1 activity was 124.86+/-66.62 U/L. No statistical difference in enzyme activity was observed between boys and girls (126.81+/-69.99 vs. 121.74+/-64.78 U/L) was observed. On the contrary, a weak negative relationship between tHcy concentration and PON1 activity was detected, with Pearson's correlation coefficient of r=-0.27. CONCLUSIONS: The significant percentage of elevated tHcy levels observed in healthy preschool cases and the negative tHcy correlation with PON1 activity are reported for the first time. Since children with a family history of cardiovascular disease have higher levels of serum Hcy, tHcy screening in children, even of this age, in relation to other parameters, such the protective PON1, might prove a useful prevention procedure for the genetic risk of premature atherosclerosis.
