Cüneyt Türkeş1, Hakan Söyüt2, Sükrü Beydemir3. 1. Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey. 2. Department of Primary Education, Faculty of Education, Bayburt University, Bayburt, Turkey. 3. Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey. Electronic address: beydemir@atauni.edu.tr.
Abstract
BACKGROUND: In this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1). METHODS: PON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography. RESULTS: The calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors. CONCLUSIONS: Our results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC(50) values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K(i) constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.
BACKGROUND: In this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1). METHODS:PON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography. RESULTS: The calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors. CONCLUSIONS: Our results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC(50) values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K(i) constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.
Authors: Giuseppe Derosa; Amedeo Mugellini; Rosa Maria Pesce; Angela D'Angelo; Pamela Maffioli Journal: Medicine (Baltimore) Date: 2016-03 Impact factor: 1.889