Some cardiovascular therapeutics inhibit paraoxonase 1 (PON1) from human serum

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 0.012 μM, 0.621 μM, 0.672 μM, 1.462 μM, 3.255 μM, 4.495 μM and 47.803 μM, respectively, and Ki constants were calculated to be 0.035 ± 0.01273 μM, 1.115 ± 0.27003 μM, 1.188 ± 0.11529 μM, 3.104 ± 1.00478 μM, 5.427 ± 1.34063 μM, 10.7 ± 3.14572 μM and 109 ± 17.47875 μM, 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.