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Abstract Title:

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

Abstract Source:

Eur J Pharmacol. 2010 Oct 25;645(1-3):135-42. Epub 2010 Jul 27. PMID: 20670621

Abstract Author(s):

Mehmet Mustafa Işgör, Sükrü Beydemir

Article Affiliation:

Atatürk University, Faculty of Sciences, Department of Chemistry, Biochemistry Division, 25240, Erzurum, Turkey.

Abstract:

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. IC(50) values and K(i) constants were calculated for digoxin, metoprolol tartrate, verapamil, diltiazem, amiodarone, dobutamine, and methylprednisolone, which show inhibitory effects. IC(50) values were determined to be 0.012 microM, 0.621 microM, 0.672 microM, 1.462 microM, 3.255 microM, 4.495 microM and 47.803 microM, respectively, and K(i) constants were calculated to be 0.035+/-0.01273 microM, 1.115+/-0.27003 microM, 1.188+/-0.11529 microM, 3.104+/-1.00478 microM, 5.427+/-1.34063 microM, 10.7+/-3.14572 microM and 109+/-17.47875 microM, respectively. A comparison of the IC(50) and K(i) 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.

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