Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies

Epilepsy Res. 2019 Jul:153:7-13. doi: 10.1016/j.eplepsyres.2019.03.009. Epub 2019 Mar 15.

Abstract

Background and aims: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam.

Method: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0.

Results: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group.

Conclusion: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Keywords: 8-OHdG; Carnitine; Epilepsy; Levetiracetam; Oxidative stress; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Anticonvulsants
  • Carnitine / blood*
  • Child
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Levetiracetam / adverse effects*
  • Lipid Peroxidation / drug effects*
  • Liver / drug effects*
  • Liver Function Tests
  • Male
  • Malondialdehyde / metabolism
  • Retrospective Studies
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Valproic Acid / adverse effects*

Substances

  • Anticonvulsants
  • Thiobarbituric Acid Reactive Substances
  • Levetiracetam
  • Malondialdehyde
  • Valproic Acid
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Carnitine