Antiepileptic drugs: Impacts on human serum paraoxonase‐1 |
| |
| Authors: | Şükrü Beydemir Yeliz Demir |
| |
| Affiliation: | 1. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eski?ehir, Turkey;2. Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey |
| |
| Abstract: | Serum paraoxonase (PON1) is a key enzyme related to high‐density lipoprotein (HDL)‐cholesterol particle. It can prevent the oxidation of low‐density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC50 values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. Ki constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive. |
| |
| Keywords: | antiepileptic drug, enzyme inhibition enzyme purification paraoxonase |
|
|
