Article Text

  1. I Berger1,
  2. I Segal2,
  3. D Shmueli3,
  4. A Saada-Reisch4
  1. 1Neuro-Pediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel,
  2. 2Hebrew University Medical School, Jerusalem, Israel,
  3. 3Child Development Center, Kupat Cholim Clalit, Jerusalem, Israel,
  4. 4Metabolic Disease Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel


Objective: One of the mechanisms causing adverse effects of anti-epileptic drugs (AED) is the inhibition of mitochondrial oxidative phosphorylation (OXPHOS). Most studies discuss valproic acid, the knowledge regarding other AED is scarce. We have investigated: the effect of other AED on the OXPHOS process in children; a simple method to measure this effect in peripheral white blood cells (WBC).

Methods: Mitochondrial OXPHOS evaluated by measuring enzymatic activities of complexes II–IV and by measuring mitochondrial adenosine triphosphate (ATP) production in WBC of five epileptic children treated by a single AED. The results were compared with healthy individuals. Blood samples were taken before treatment initiation and repeated during the following 24 months.

Results: In the carbamazepine-treated children decrease in ATP production and increase in complex II activity were measured. In the phenobarbital treated: increase in ATP production and in complex II activity. In the lamotrigine treated: increase in ATP production without change in respiratory chain enzyme activity.

Conclusions: AED affecting the mitochondrial OXPHOS process. Each AED caused a different effect. In this pilot study phenobarbital and lamotrigine significantly increased mitochondrial ATP production while carbamazepine had a significant negative influence. This study is unique because the effects of AED on mitochondrial OXPHOS were mostly done in animal models studying mainly the effect of valproic acid. Moreover, this work demonstrated that the evaluation can be performed in humans by relatively simple methods, using small samples of peripheral blood. Further expanded studies are needed including larger cohorts and additional drugs.

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