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. IC 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. K 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.

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors

“…In this study was applied the same procedure with our previous studies and PON1 was purified from human serum in three simple chromatographic steps. These results confirm the findings of a great deal of the previous works . After, the pantoprazole, omeprazole and esomeprazole as PPIs were tested on paraoxonase activity of the PON1 enzyme.…”

“…These enzymes have been purified from different tissues. Drug interactions studies of these essential enzymes have made significant contributions to the academic literature in the field of drug metabolism . For instance, we purified PON1 enzyme from human serum by using chromatographic methods.…”

Evaluation of chalcones as inhibitors of glutathione S‐transferase

“…According to Laemmli's procedure, the purity and presence of GST was observed by the SDS‐PAGE technique. The method was performed according to our previous studies . After this procedure, a single band was seen for GST.…”

The effects of zingerone against vancomycin‐induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes

“…PON1 is an antioxidant enzyme, which serves as by protecting low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) from oxidative stress . It is well known that there is a relationship between oxidative stress and some vascular diseases, including atherosclerosis and cancer …”