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

Isgor M. M., BEYDEMİR Ş.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.645, no.1-3, pp.135-142, 2010 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 645 Issue: 1-3
  • Publication Date: 2010
  • Doi Number: 10.1016/j.ejphar.2010.07.030
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.135-142
  • Anadolu University Affiliated: No


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 K-i 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 mu M, 0.621 mu M, 0.672 mu M, 1.462 mu M, 3.255 mu M, 4.495 mu M and 47.803 mu M, respectively, and K-i constants were calculated to be 0.035 +/- 0.01273 mu M, 1.115 +/- 0.27003 mu M, 1.188 +/- 0.11529 mu M, 3.104 +/- 1.00478 mu M, 5.427 +/- 1.34063 mu M, 10.7 +/- 3.14572 mu M and 109 +/- 17.47875 mu M, respectively. A comparison of the IC50 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. (C) 2010 Elsevier B.V. All rights reserved.