title: Antiepileptic drugs: Impacts on human serum paraoxonase-1.
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. IC50values 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. Kiconstants 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, 26470, Turkey.
authors.forename: Şükrü
authors.initials: Ş
authors.lastname: Beydemir
authors.affiliation: Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, 25240, Turkey.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Demir
mesh_terms: D000588:Amines / Q000009:adverse effects / Q000494:pharmacology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000077206:Gabapentin; D006801:Humans; D007700:Kinetics; D000077287:Levetiracetam; D010672:Phenytoin / Q000009:adverse effects / Q000494:pharmacology; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D011324:Primidone / Q000009:adverse effects / Q000494:pharmacology; D014421:Turkey; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D011324:Primidone; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; D000077206:Gabapentin; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D010889:Piracetam
keywords: antiepileptic drug, enzyme inhibition; enzyme purification; paraoxonase