Akademik Veri Yönetim Sistemi
European Journal of Pharmacology, cilt.645, sa.1-3, ss.135-142, 2010 (SCI-Expanded)
Harel et al. (2004) report that atherosclerosis is the underlying cause for 50% of the mortality in Western societies, and organophosphates in nature constitute an important risk as well as a terrorist threat for all living things. Since paraoxonase enzyme (PON) is a bioscavenger against both atherosclerosis and organophosphate toxicity, studies on paraoxonase enzyme (PON) occupy an important place in the scientific world. In this study, we purified PON1 enzyme from human serum by using a simple three-step purification method: ammonium sulfate precipitation, ion-exchange chromatography and gel filtration chromatography. In addition, we investigated the effects of certain cardiovascular drugs on human serum paraoxonase enzyme activity. IC50 values and Ki constants were calculated for digoxin, metoprolol tartrate, verapamil, diltiazem, amiodarone, dobutamine, and methylprednisolone, which show inhibitory effects. IC50 values were determined to be 0.012μM, 0.621μM, 0.672μM, 1.462μM, 3.255μM, 4.495μM and 47.803μM, respectively, and Ki constants were calculated to be 0.035±0.01273μM, 1.115±0.27003μM, 1.188±0.11529μM, 3.104±1.00478μM, 5.427±1.34063μM, 10.7±3.14572μM and 109±17.47875μM, respectively. A comparison of the IC50 and Ki values of the drugs revealed that digoxin has the maximum inhibition rate. Furthermore, methylprednisolone and amiodarone were found to be competitive inhibitors, verapamil and dobutamine were uncompetitive inhibitors, while others inhibited the enzyme in noncompetitive manner. © 2010 Elsevier B.V.