Effects of antiepileptic drugs on mitochondrial functions, morphology, kinetics, biogenesis, and survival

Effects of antiepileptic drugs on mitochondrial functions, morphology, kinetics, biogenesis, and survival

Author Finsterer, Josef Google Scholar
Scorza, Fulvio A. Autor UNIFESP Google Scholar
Abstract Objectives: Antiepileptic drugs (AEDs) exhibit adverse and beneficial effects on mitochondria, which have a strong impact on the treatment of patients with a mitochondrial disorder (MID) with epilepsy (mitochondrial epilepsy). This review aims at summarizing and discussing recent findings concerning the effect of AEDs on mitochondrial functions and the clinical consequences with regard to therapy of mitochondrial epilepsy and of MIDs in general. Methods: Literature review. Results: AEDs may interfere with the respiratory chain, with non-respiratory chain enzymes, carrier proteins, or mitochondrial biogenesis, with carrier proteins, membrane-bound channels or receptors and the membrane potential, with anti-oxidative defense mechanisms, with morphology, dynamics and survival of mitochondria, and with the mtDNA. There are AEDs of which adverse effects outweigh beneficial effects, such as valproic acid, carbamazepine, phenytoin, or phenobarbital and there are AEDs in which beneficial effects dominate over mitochondrial toxic effects, such as lamotrigine, levetiracetam, gabapentin, or zonisamide. However, from most AEDs only little is known about their interference with mitochondria. Conclusions: Mitochondrial epilepsy might be initially treated with AEDs with low mitochondrial toxic potential. Only in case mitochondrial epilepsy is refractory to these AEDs, AEDs with higher mitochondrial toxic potential might be tried. In patients carrying POLG1 mutations AEDs with high mitochondrial toxic potential are contraindicated.
Keywords side effects
toxicity
epilepsy
antiepileptic drugs
mitochondrion
reactive oxygen species
apoptosis
membrane potential
oxidative stress
respiratory chain
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Date 2017
Published in Epilepsy Research. Amsterdam, v. 136, p. 5-11, 2017.
ISSN 0920-1211 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 5-11
Origin http://dx.doi.org/10.1016/j.eplepsyres.2017.07.003
Access rights Closed access
Type Article
Web of Science ID WOS:000412255800002
URI https://repositorio.unifesp.br/handle/11600/57271

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