Karabiber H.Yakinci C.Durmaz Y.Temel I.Mehmet N.2024-08-042024-08-0420040387-7604https://doi.org/10.1016/S0387-7604(03)00076-7https://hdl.handle.net/11616/90643In experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66±2.11?mol/l and 69.35±23.20?mol/l, 1.89±1. 01?mol/l and 49.39±10.61?mol/l in the carbamazepine group, and 1.22±0.55?mol/l, 29.53±10.05?mol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P<0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P<0.01), however, there was no statistically significant difference in the levels of nitrite (P>0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide. © 2003 Elsevier B.V. All rights reserved.Patients:95 children (52 boys, 43 girls) with an age range of 2 to 17 were included in the study. 23/95 were given Tegretol (13 boys, 10 girls) with a mean age of 9.45 ± 3.73, 34/95 were given valproic acid (17 boys, 17 girls) with a mean age of 7.90 ± 3.93 and 38/95 served as controls (epileptic children who had take antiepileptic drugs previously but were followed up without any medication) (22 boys, 16 girls) with a mean age of 9.01 ± 3.57TypeofStudy:The objective of this comparative, controlled clinical study was to investigate the effects of valproic acid (VPA) and Tegretol on the levels of nitrite and nitrate as an indicator of nitric oxide (NO) level in epileptic children.DosageDuration:Dosage not stated. Duration of treatment at least 6 months.ComparativeDrug:Valproic acid (dose not stated, duration of treatment was for at least 6 months).Results:In the valproic acid group serum nitrite and nitrate levels were 2.66 ± 2.11 mcmol/l and 69.35 ± 23.20 mcmol/l, 1.89 ± 1.01 mcmol/l and 49.39 ± 10.61 mcmol/l in the Tegretol group, and 1.22 ± 0.55 mcmol/l, 29.53 ± 10.05 mcmol in the control group, respectively. Serum nitrite and nitrate levels of both VPA and Tegretol groups were found to be significantly higher than the control group statistically (P < 0.01). When VPA and Tegretol groups were compared to each other, no statistically significant difference could be found in the nitrite levels (P > 0.05), however, nitrate levels of VPA group were found to be statistically significantly higher than the Tegretol group (P < 0.01). Routine biochemical parameters (fasting glucose level, urea, creatinine, AST, ALT, ALP) and complete blood count values were in normal ranges both in antiepileptic users and the control group and no difference could be found between the groups statistically. When NO and drug levels in the blood were compared, there was no statistically significant correlation between them.AdverseEffects:No adverse events were mentioned.AuthorsConclusions:Although carbamazepine and VPA are effective in different ways, nitrite and nitrate levels were found to be higher in both groups in our study when compared to the control group. Since liver, kidney and heart diseases that could elevate nitrite and nitrate levels were excluded previously, the results obtained reflect the data of epileptic patients. With reference to the fact that high levels of nitric oxide have an anticonvulsive effect, the antiepileptic effect of VPA and carbamazepine might be through elevating the level of NO directly or indirectly. When VPA and carbamazepine groups were compared to each other, there were no statistical differences between nitrite levels, however, nitrate levels in the VPA group were found to be significantly higher. VPA may have a stronger effect on NO synthesis than Tegretol and may use NO synthesis pathway more in demonstrating its anticonvulsive effect. Even though the cause of increase in the level of NO cannot be explained clearly, it can be suggested that VPA and carbamazepine might have antiepileptic effects through nitric oxide. Further studies dealing with antiepileptic drugs and NO levels and a more clear demonstration of the relation may lead to new treatment methods in refractory epileptics.FreeText:The children had been diagnosed as having epilepsy according to the clinical and electroencephalographic (EEG) findings and had been followed at least for 6 months. Treatment group included children taking Tegretol or VPA regularly at least for the last 6 months and the control group comprised of children who had taken antiepileptic medication previously and did not get any treatment at least for the last 6 months and had no convulsion as well. All children were evaluated in the aspects of mental-motor retardation, renal or hepatic disorders, heart diseases and hypertension. After getting consent of the families, systemic complaints of the children were inquired prior to the study and physical examinations, complete blood count, hepatic and renal function tests were carried out and Tegretol or VPA levels in the blood were measured as well. Fasting blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, creatinine, Na, K, Cl , Ca and other routine biochemical analyses were also determined. Following the deproteinization of all samples by adding NaOH/ZnSO4, nitrite and nitrate levels were analyzed together. Nitrite was analyzed directly, however, nitrate was first transformed to nitrite by cadmium reduction and then analyzed by the same method. Results were analyzed using statistical analysis. Serum nitrite and nitrate levels were compared among VPA, Tegretol and control groups by one-way analysis of variance (ANOVA).Indications:23 patients with epilepsy (2/23 tonic, 3/23 atonic, 4/23 complex partial and 14 generalized tonic clonic seizures).eninfo:eu-repo/semantics/closedAccessCarbamazepineEpileptic childrenNitric oxideValproic acidArticle261151810.1016/S0387-7604(03)00076-72-s2.0-0346461490Q2