Effects of valproate, carbamazepine, and levetiracetam on the antioxidant and oxidant systems in epileptic patients and their clinical importance.
OBJECTIVE
This study was carried out to determine the effects of valproate (VPA), carbamazepine, and levetiracetam (LEV) on antioxidant and oxidant enzyme activities and the clinical importance of these effects.


METHODS
We enrolled 32 patients receiving VPA, 17 receiving carbamazepine, 8 receiving LEV, 11 on multidrug therapy, and 30 sex- and age-matched healthy volunteers. We measured the serum activities of paraoxonase and arylesterase and the levels of 8-hydroxyguanine (8-OHG) and oxidized low-density lipoprotein in all the subjects. We also determined the clinical features of the patients.


RESULTS
The serum paraoxonase and arylesterase activities were significantly lower (P = 0.003 and P = 0.0001, respectively), and the oxidized low-density lipoprotein and 8-OHG levels were higher (P = 0.029 and P = 0.0001, respectively) in the patients than in the controls. The serum antioxidant activity was low, and the oxidant activity was high in the monotherapy patients (P < 0.05). Comparing the monotherapy with the polytherapy, only the combination of VPA-LEV was associated with a high 8-OHG level (P = 0.04). The serum 8-OHG level was higher in the patients taking antiepileptic drugs (AEDs) for the first 2 months than in the controls (P = 0.0001) and positively correlated with the duration of epilepsy (r = 0.387, P < 0.01).


CONCLUSIONS
Oxidative stress is seen in each of the AEDs after the first 2 months. There was no dominance of the monotherapy over the polytherapy, except for the VPA-LEV combination. None of the patients' characteristic features were related to oxidative damage, except for the duration of the epilepsy and the AED therapy.
Varoglu
Asuman Orhan
AO
Department of Neurology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. asumanorhan@yahoo.com
Yildirim
Abdulkadir
A
Aygul
Recep
R
Gundogdu
Omer Lutfi
OL
Sahin
Yasar Nuri
YN
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002220:Carbamazepine / Q000494:pharmacology* / Q000627:therapeutic use; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D000077287:Levetiracetam; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D000975:Antioxidants; D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002220:Carbamazepine; D000077287:Levetiracetam; C024829:8-hydroxyguanine; D006147:Guanine; D014635:Valproic Acid; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D010889:Piracetam